Abstract
Synopsis: Captopril1 is the first orally active inhibitor of angiotensin -converting enzyme to become available. It has been studied to date primarily in hypertension. In mild to moderate essential hypertension Captopril is about as effective as usual doses of hydrochlorothiazide or Propranolol, about one-half of such patients needing the addition of a diuretic to achieve satisfactory control of blood pressure. In severe hypertension Captopril plus a diuretic (and in some patients a βr-blocker) usually reduced blood pressure significantly more than could be achieved with ‘standard triple therapy’ in patients not responding adequately to such a regimen, and often resulted in an improved feeling of well-being in severely hypertensive patients previously receiving intensive multiple drug therapy. Indeed, at the present stage of the drug’s development, patients not responding to or not tolerating ‘traditional’ antihypertensive therapy represent the most suitable candidates for Captopril treatment. While Captopril has been well tolerated in most patients, some troublesome or potentially serious side effects have been reported, including agranulocytosis, dysgeusia and reduced renal function; although a clear causal relationship with Captopril was not always established, it would appear that the final place of Captopril in the treatment of hypertension may ultimately depend on further clarification of its adverse effects profile. In addition to studies in hypertension, Captopril has produced encouraging improvement in a small number of patients with severe congestive heart failure resistant to conventional therapy. Captopril must be considered an exciting addition to the therapeutic armamentarium; it, and pharmacologically related compounds of the future, will continue to generate much interest as their final place in therapy becomes better defined through additional well designed studies and wider clinical experience.
Pharmacodynamic Studies: Captopril is an orally active inhibitor of angiotensin-converting enzyme, the enzyme responsible for conversion of inactive angiotensin I to the potent vasopressor angiotensin II. In animal studies and in man Captopril has been shown to increase plasma renin activity, to decrease plasma concentrations of angiotensin II and aldosterone, and to antagonise the pressor response to exogenous angiotensin I. Such effects were most pronounced in subjects with high pretreatment plasma renin concentrations.
Since angiotensinrconverting enzyme is synonymous with kininase II (one of the enzymes responsible for the degradation of bradykinin into inactive fragments), some effects of Captopril on the kallikrein-kinin-prostaglandin system could be anticipated. In both animals and man Captopril reduced urinary kallikrein excretion, and potentiated the effects of exogenous bradykinin, and in animals ‘higher’ doses (about 20 to 30mg/kg/day orally in rats and dogs) increased blood bradykinin concentration and urinary kinin excretion. Some studies have reported evidence that Captopril may also stimulate Prostaglandin production or release, but results of such studies were often divergent and further studies are needed to clarify the significance of any Prostaglandin-mediated effects in man. Indeed, the relative importance of all the effects described above to the blood pressure-lowering effect of Captopril is the subject of continuing discussion and investigation. Thus, while inhibition of angiotensin-converting enzyme is probably of major importance to captopril’s blood pressure-lowering effect, it is not clear what aspect of angiotensin-converting enzyme inhibition is of primary importance.
Captopril produced a rapid, marked reduction in blood pressure in animal models of hypertension thought to be dependent on the renin-angiotensin system (2-kidney renal hypertension, and hypertension secondary to aortic stricture in rats), and administered alone or in combination with hydrochlorothiazide it prolonged survival time in such animals. In animal hypertension models thought not to be dependent on the renin angiotensin system (1-kidney renal hypertension, or steroid/salt hypertension in rats) Captopril produced a smaller and more gradual reduction in blood pressure. Similarly, in genetic (spontaneous) hypertension in rats, considered a model for essential hypertension in man, Captopril produced a gradual, progressive reduction in blood pressure over weeks to months during continuous administration. (The acute response to a single dose of Captopril in this model was attenuated by prior bilateral nephrectomy in most, but not all, studies.) Prophylactic Captopril administration to young genetically hypertensive rats prevented or partially suppressed the development of hypertension, depending on the doses used.
In most short term pharmacodynamic studies Captopril had no significant effects on cardiac function, but during chronic administration to patients with hypertension it usually reduced systemic vascular resistance (18 to 30%) and slightly increased cardiac output (about 15%), without altering heart rate. In patients with severe congestive heart failure acute administration of Captopril (25 to 150mg) had beneficial cardiovascular effects, for example reducing systemic and pulmonary vascular resistance (30 to 40%) and pulmonary wedge pressure (30 to 50%) and increasing cardiac output (about 20%). The effect on heart rate in such patients was not consistent, the rate significantly decreasing in some studies (by about 10 to 20%) but remaining unaltered in others.
In animal studies, and in a few small studies reporting such data in hypertensive patients, renal blood flow usually increased during Captopril administration. However, the effect on glomerular filtration rate was less consistent, and thus further studies are needed to clarify captopril’s effect on renal function under conditions of clinical use.
Pharmacokinetic Studies: Pharmacokinetic data for Captopril in man are limited. About 70% of an oral dose is absorbed by healthy subjects. The drug is about 30% bound to plasma protein. Captopril does not appear to enter readily into the central nervous system or into breast milk. More than 30% of an oral dose is excreted unchanged in the urine, about another 30% appearing in the urine as polar metabolites. In patients with renal dysfunction the overall (Captopril plus metabolites) elimination rate correlated closely with Creatinine clearance; the dose should be appropriately reduced in patients with moderate to severe renal impairment.
Therapeutic Trials: In open studies in patients with essential or renovascular hypertension, often not responding to ‘optimal conventional therapy’, Captopril (usually 200 to 400mg daily) reduced both systolic and diastolic blood pressure by about 20 to 25% in responding patients; about 50% or more of these moderately to severely hypertensive patients required the addition of a diuretic for satisfactory blood pressure control. In placebo comparisons, Captopril (usually up to 450mg daily) reduced systolic and diastolic pressures by about 15 to 25% in mild to moderate essential or renovascular hypertension, or in a few patients with hypertension related to chronic renal failure, but as in open studies ‘satisfactory’ blood pressure control often required the addition of a diuretic. In patients treated for ‘longer’ periods in such studies there was no evidence of decreased effectiveness of Captopril after periods of up to 2 years. In single-blind comparative studies with other antihypertensive drugs, Captopril, hydrochlorothiazide (up to 100mg daily) or Propranolol (up to 360mg daily) were about equally effective in patients with mild to moderate essential or renovascular hypertension. In severe resistant hypertension Captopril alone usually lowered blood pressure to about the same level as with standard ‘triple therapy’ (consisting of hydrochlorothiazide 100mg, Propranolol 320mg and hydralazine 200mg daily), but neither treatment adequately controlled blood pressure in most of these ‘resistant’ patients. However, a combination of Captopril plus a diuretic, and in some patients a βr-blocker, usually reduced blood pressure more than was achieved with standard triple therapy, although a small number of patients could not be adequately controlled on any combination used.
Although in most studies in patients with hypertension Captopril was given in 3 or 4 divided doses, there is some evidence that twice daily administration provides adequate blood pressure control throughout the day.
The relationship between pretreatment plasma renin activity and blood pressure-lowering response to Captopril is somewhat unsettled, some authors reporting a close correlation and others finding none. However, when results of a multicentre study were pooled, an increased response in high renin patients was apparent, although Captopril may lower blood pressure also in normal or low renin states.
In addition to studies in hypertension, a few small studies in severe treatment-resistant congestive heart failure have shown encouraging improvement in indexes of cardiac function (cardiac output, cardiac index, stroke volume, and ejection fraction increased; pulmonary resistance, and left ventricular end diastolic dimension decreased), and in exercise performance (exercise time usually increased by about 50 to 60%) and symptomatology in patients receiving Captopril 25 to 150mg 3 times daily for up to 6 months.
Side Effects: The most frequent side effects with Captopril are skin rash (about 14% of patients overall), sometimes severe and accompanied by fever, and taste disturbances (about 6% of patients). Both reactions were readily reversible on discontinuing treatment or reducing the dose, and in some cases were resolved despite continued treatment at the same dosage. Reversible agranulocytosis has occurred within the first 3 months in a small number of patients receiving Captopril; although most such patients had complex medical histories and were receiving multiple drug therapy, 1 patient with renovascular hypertension was otherwise well. In all patients the time course of development and subsequent resolution of the condition suggests an association with Captopril treatment.
Reversible deterioration in renal function (accompanied by hyperkalaemia in 1 patient) occurred in a few patients with pre-existing renal disease, or renal transplants, receiving widely varying doses of Captopril (25 to 450mg daily). A clear relationship to Captopril was demonstrated by rechallenge in 1 patient. Whether such changes were due to a nephrotoxic effect of the drug or were secondary to haemodynamic changes is unclear. Proteinuria occurred in about 2% of patients treated for 8 months or more, and the nephrotic syndrome, and/or evidence of membranous glomerulopathy, have been reported in a small number of patients receiving Captopril.
Tachycardia on standing has occasionally occurred, and chest pain and acute myocardial infarction have been reported in isolated individuals during treatment with Captopril. Postural hypotension has not been a common problem during Captopril treatment.
Dosage and Administration: During Captopril therapy urinary protein loss and haematological status should be monitored periodically. In the presence of sodium depletion (which would include some patients receiving a diuretic) the first few doses may produce dramatic reductions in blood pressure. Since Captopril may increase serum potassium concentrations, potassium supplements or potassium-sparing diuretics should be used only if clearly required, and then with caution.
In hypertension treatment may be initiated with 25mg 3 times daily taken on an empty stomach, increasing to 50mg 3 times daily after 1 to 2 weeks if required. After a further 1 to 2 weeks a diuretic may be added in gradual dosage increments if necessary. If response is inadequate when the usual maximum dosage of the diuretic is reached, the Captopril dose may be further increased in increments to a maximum of 150mg 3 times daily, with continued administration of the diuretic. If rapid blood pressure reduction is necessary the dose of Captopril may be increased at 24-hour intervals, but a maximum dose of 450mg daily should not be exceeded.
In severe congestive heart failure dosage is gradually titrated from a starting dose of 25mg 3 times daily (a lower dose may be effective in some patients) to a maximum of 150mg 3 times daily during continued digitalis and diuretic therapy.
In the presence of moderate to severe renal dysfunction, once the dose has been titrated to achieve the desired clinical effect the dosage interval should be extended according to guidelines based on the extent of renal impairment.
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References
Abe, K.; Itoh, T.; Satoh, M; Haruyama, T.; Imai, Y.; Goto, T.; Satoh, K.; Otsuka, Y. and Yoshinaga, K.: Indomethacin (ind) inhibits an enhanced renin release following the Captopril, SQ 14225, administration. Life Sciences 26: 561–565 (1980a).
Abe, K.; Itoh, T.; Imai, Y.; Sato, M.; Haruyama, T.; Sakurai, Y.; Goto, T.; Otsuka, Y. and Yoshinaga, K.: Implication of endogenous Prostaglandin system in the antihypertensive effect of Captopril, SQ-14225, in low renin hypertension. Japanese Circulation Journal 44: 422–425 (1980b).
Ader, R.; Chatterjee, K.; Ports, T.; Hiramatsu, B. and Parmley, W.: Beneficial hemodynamic effects of angiotensin converting enzyme inhibitor in chronic refractory heart failure. American Journal of Cardiology 43: 404 (1979a).
Ader, R.; Chatterjee, K.; Ports, T.; Hiramatsu, B.; Brundage, B. and Parmley, W.: Sustained beneficial hemodynamic effects of long term oral angiotensin converting enzyme inhibitor in chronic heart failure. Circulation 59 and 60(Suppl. 2): 130 (1979b).
Ader, R.; Chatterjee, K.; Ports, T.; Brundage, B.; Hiramatsu, B. and Parmley, W.: Immediate and sustained hemodynamic and clinical improvement in chronic heart failure by an oral angiotensin-converting enzyme inhibitor. Circulation 61: 931–937 (1980).
Aguilera, C. and Catt, K.J.: Regulation of aldosterone secretion of the renin-angiotensin system during sodium restriction in rats. Proceedings of the National Academy of Science 75: 4057–4061 (1978).
Amann, F.W.; Buhler, F.R.; Conen, D.; Brunner, F.; Ritz, R. and Speck, B.: Captopril-associated agranulocytosis. Lancet 1: 150 (1980).
Anderson, G.H.; Springer, J.; Tivnan, E.; Kearney, M. and Streeten, D.H.P.: Hypotensive mechanism of Captopril. Clinical Research 28: 328A (1980).
Andrews, D.I.: Effects of saralasin and Captopril on the blood pressure of conscious genetically hypertensive and normotensive rats. Medical Journal of Australia 2(Suppl., No.8): 7–9 (1979).
Antonaccio, M.J.; Rubin, B.; Horovitz, Z.P.; Laffan, R.J.; Goldberg, M.E.; High, J.P.; Harris, D.N. and Zaidi, I.: Effects of chronic treatment with Captopril (SQ 14225), an orally active inhibitor of angiotensin I-converting enzyme, in spontaneously hypertensive rats. Japanese Journal of Pharmacology 29: 285–294 (1979a).
Antonaccio, M.J.; Rubin, B.; Horovitz, Z.P.; Mackaness, G. and Panasevich, R.: Long-term efficacy of Captopril (SQ 14225) in 2-kidney renal hypertensive rats. Clinical and Experimental Hypertension 1: 505–519 (1979b).
Antonaccio, M.J.; High, J.P.; Rubin, B. and Schaeffer, T.: Contribution of the kidneys but not adrenal glands to the acute antihypertensive effects of Captopril in spontaneously hypertensive rats. Clinical Science 57: 127S–130S (1979c).
Asaad, M.M. and Antonaccio, M.J.: The effects of Captopril (SQ 14,225) on vascular tissue renin in spontaneously hypertensive (SHR) and WKY—normotensive (NTR) rats: relationship to systolic blood pressure (SBP) and plasma renin activity (PRA). Pharmacologist 21: 212 (1979).
Atkinson, A.B. and Robertson, J.I.S.: Captopril in the treatment of clinical hypertension and cardiac failure. Lancet 2: 836–839 (1979).
Atkinson, A.B.; Brown, J.J.; Fraser, R.; Leckie, B.; Lever, A.F.; Morton, J.J. and Robertson, J.I.S.: Captopril in hypertension with renal artery stenosis and in intractable hypertension; acute and chronic changes in circulating concentrations of renin, angiotensins I and II and aldosterone, and in body composition. Clinical Science 57: 139S–143S (1979a).
Atkinson, A.B.; Brown, J.J.; Leckie, B.; Lever, A.F. Morton, J.J.; Fraser, R. and Robertson, J.I.S.: Captopril in a hyponatraemic hypertensive: need for caution in initiating therapy. Lancet 1: 557 (1979b).
Atkinson, A.B.; Davies, D.L.; Leckie, B.; Morton, J.J.; Brown, J.J.; Fraser, R.; Lever, A.F. and Robertson, J.I.S.: Hyponatraemic hypertensive syndrome with renal-artery occlusion corrected by Captopril. Lancet 2: 606–609 (1979c).
Atkinson, A.B.; Brown, J.J.; Fraser, R.; Leckie, B.; Lever, A.F.; Morton, J.J. and Robertson, J.I.S.: Captopril, angiotensin II, and sodium in blood-pressure regulation. Lancet 1: 1140 (1979d).
Atkinson, A.B.; Brown, J.J.; Fraser, R.; Leckie, B.J.; Lever, A.F.; McKay, A.; Morton, J.J. and Robertson, J.I.S.: Antagonists and inhibitors of the renin-angiotensin-aldosterone system in the treatment of hypertension; in Robertson and Pickering (ed.) The Therapeutics of Hypertension, pp.29–61 (Academic Press, London 1980a).
Atkinson, A.B.; Brown, J.J.; Lever, A.F.; McAreavey, D.; Robertson, J.I.S.; Behan, P.O.; Melville, I.D. and Weir, A.I.: Neurological dysfunction in two patients receiving Captopril and Cimetidine. Lancet 2: 36–37 (1980b).
Atkinson, A.B.; Lever, A.F.; Brown, J.J. and Robertson, J.I.S.: Combined treatment of severe intractable hypertension with Captopril and diuretic. Lancet 2: 105–108 (1980c).
Atlas, S.A.; Case, D.B.; Sealey, J.E.; Laragh, J.H. and McKinstry, D.N.: Interruption of the renin-angiotensin system in hypertensive patients by Captopril induces sustained reduction in aldosterone secretion, potassium retention and natriuresis. Hypertension 1: 274–280 (1979).
Awan, N.A.; Hermanovich, J.; Skinner, P. and Mason, D.T.: Captopril compared to prazosin in heart failure: equal preload reduction with dissimilar pump output effects. Circulation 59 and 60(Suppl. 2): 180 (1979a).
Awan, N.A.; Hermanovich, J.; Skinner, P.; Jpye, J.A.; DeMaria, A.N.; Bommer, W.J. and Mason, D.T.: Cardiocirculatory actions of the oral angiotensin-converting enzyme inhibitor, Captopril, in severe chronic congestive heart failure: evaluation by cardiac catheterization, echocardiography, nuclear angiography, treadmill exercise and symptomatology. Clinical Research 27: 228A (1979b).
Baker, K.M.; Vaughan, E.D.; Johns, D.W.; Ayers, C.R. and Carey, R.M.: Antihypertensive effects of angiotensin blockade: saralasin versus Captopril. Clinical Research 27: 311A (1979a).
Baker, K.M.; Johns, D.W.; Ayers, C.R.; Williams, S.C.; Yancey, M.R.; Peach, M.J. and Carey, R.M.: Comparison of Captopril (SQ 14225) with triple therapy in severe hypertension. Circulation 59 and 60(Suppl. 2): 144 (1979b).
Baker, K.M.; Johns, D.W.; Ayers, C.R. and Carey, R.M.: Ischemic cardiovascular complications concurrent with administration of Captopril. A clinical note. Hypertension 2: 73–74 (1980).
Bengis, R.G.; Coleman, T.G., Young, D.B. and McCaa, R.E.: Long-term blockade of angiotensin formation in various normotensive and hypertensive rat models using converting enzyme inhibitor (SQ 14,225). Circulation Research 43(Suppl. 1) 45–53 (1978).
Benuck, M. and Marks, N.: Inhibition of brain angiotensin-I converting enzyme by Bothrops jararaca nonapeptide (SQ -20881) and a prolyl analog (SQ -14225). Journal of Neurochemistry 30: 1653–1655 (1978).
Bravo, E.L. and Tarazi, R.C.: Converting enzyme inhibition with an orally active compound in hypertensive man. Hypertension 1: 39–46 (1979).
Brunner, H.R.; Gavras, H.; Turini, G.S.; Waeber, B.; Chappuis, P. and McKinstry, D.N.: Long-term treatment of hypertension in man by an orally active angiotensin-converting enzyme inhibitor. Clinical Sciences and Molecular Medicine 55: 293s–295s (1978a).
Brunner, H.R.; Wauters, J.P.; McKinstry, D.; Waeber, B.; Turini, G. and Gavras, H.: Inappropriate renin secretion unmasked by Captopril (SQ 14225) in hypertension of chronic renal failure. Lancet 2: 704–707 (1978b).
Brunner, H.R.; Gavras, H.; Waeber, B.; Kershaw, G.R.; Turini, G.A.; Vukovich, R.A.; McKinstry, D.N. and Gavras, I.: Oral angiotensin-converting enzyme inhibitor in long-term treatment of hypertensive patients. Annals of Internal Medicine 90: 19–23 (1979a).
Brunner, H.R.; Gavras, H.; Waeber, B.; Turini, G.A.; McKinstry, D.N.; Vokovich, R.A. and Gavras, I.: Orally active angiotensin-converting enzyme inhibitor (SQ 14,225) as a treatment for essential hypertension. British Journal of Pharmacology 7(Suppl. 2): 205S–211s (1979b).
Brunner, H.R.; Waeber, B. and Gavras, H.: Rational use of Captopril. Lancet 1: 832 (1979c).
Brunner, H.R.; Gavras, H.; Waeber, B.; Textor, S.C.; Turini, G.A. and Wanters, J.P.: Clinical use of an orally acting converting enzyme inhibitor: Captopril. Hypertension 2: 558–566 (1980).
Case, D.B.; Attas, S.A.; Laragh, J.H.; Sealey, J.E.; Sullivan, P.A. and McKinstry, D.N.: Clinical experience with blockade of the renin-angiotensin-aldosterone system by an oral converting-enzyme inhibitor (SQ 14,225, Captopril) in hypertensive patients. Progress in Cardiovascular Diseases 21: 195–206 (1978).
Case, D.B.; Attas, S.A.; Sullivan, P. and Laragh, J.H.: Successful acute and chronic treatment of severe and malignant hypertension with oral converting enzyme inhibitor Captopril. Circulation 59 & 60(Suppl. 2): 130 (1979).
Case, D.B.; Atlas, S.A.; Laragh, J.H.; Sullivan, P.A. and Sealey, J.E.: Use of first-dose response or plasma renin activity to predict the long-term effect of Captopril: Identification of triphasic pattern of blood pressure response. Journal of Cardiovascular Pharmacology 2: 339–346 (1980a).
Case, D.B.; Atlas, S.A.; Mouradian, J.A.; Fishman, R.A.; Sherman, R.L. and Laragh, JH.: Proteinuria during long-term Captopril therapy. Journal of the American Medical Association 244: 346–349 (1980b).
Cody, R.J.; Tarazi, R.C.; Bravo, E.L. and Fouad, F.M.: Haemodynamics of orally-active converting enzyme inhibitor (SQ 14225) in hypertensive patients. Clinical Science and Molecular Medicine 55: 453–459 (1978).
Collste, P.; Haglund, K.; Lundgren, G.; Magnusson, G. and Ostman, J.: Reversible renal failure during treatment with Captopril. British Medical Journal 2: 612–613 (1979).
Crantz, F.R.; Swartz, S.L.; Hollenberg, N.K.; Moore, T.J.; Deuhy, R.G.; Levine, L. and Williams, G.H.: Role of Prostaglandins in the hypotensive response to Captopril in essential hypertension. Clinical Research 27: 592A (1979).
Crofton, J.T.; Share, L. and Horovitz, Z.P.: The effect of SQ 14,225 on systolic blood pressure and urinary excretion of Vasopressin in the developing spontaneously hypertensive rat. Hypertension 1: 462–467 (1979).
Cunningham, R.J. and Brouhard, B.H.: Captopril and kallikrein. Lancet 1: 832 (1980).
D’Angelo, W.A.; Lopez-Ovejero, J.A.; Saal, S.D. and Laragh, J.H.: Early versus late treatment of scleroderma renal crisis and malignant hypertension with Captopril. Arthritis and Rheumatism 23: 664 (1980).
Davis, R.; Ribner, H.S.; Keung, E.; Sonnenblick, E.H. and Le-Jemtel, T.H.: Treatment of chronic congestive heart failure with Captopril, an oral inhibitor of angiotensin-converting enzyme. New Zealand Journal of Medicine 301: 117–121 (1979).
Dean, AV., Kripalani, K.J. and Migdalof, B.H.: Disposition of Captopril (SQ 14,225) in spontaneously hypertensive and normotensive rats. Federation Proceedings 38: 743 (1979).
Dean, H.G. and Ingham, S.: The effect f SQ 14225 on fluid intake in DOCA/salt hypertensive rats. British Journal of Pharmacology 64: 390P–391P (1978).
de Bruyn, B.J.H.; Verhoeven, R.P.; Boomsa, F.; Man in’t Veld, A.J.; Wenting, G.J. and Schalekamp, M.A.D.H.: Long-term effects of ‘converting enzyme’ inhibition on systemic and renal haemodynamics, body fluid volumes and plasma-noradrenaline in essential hypertension. Proceedings of the 6th Scientific Meeting of the International Society of Hypertension, Goteborg, Sweden, June 11–13 (1979).
de Jong, W. and ten Berg, R.G.: Importance of the enhanced secretion of renin in the augmented blood pressure rise after reapplication of renal artery clip. 3rd European Colloquium on Renal Physiology, Saltsjoben, Sweden, June 17–20 (1979).
Devlin, R.G. and Fleiss, P.M.: Selective resistance to the passage of Captopril into human milk. Clinical Pharmacology and Therapeutics 27: 250 (1980).
Dollery, C.T. and Miyamori, I.: Indomethacin and the hypotensive action of Captopril in DOCA salt hypertensive rats. British Journal of Clinical Pharmacology 68: 117P–118P (1980).
Donker, J.M.; Prins, E.J.L. and Hoorntje, S.J.: The responsiveness to exogenous angiotensin I (AI), angiotensin II (AII) and bradykinin (BK) after incremental doses of Captopril (SQ 14, 225). Kidney International 16: 904 (1979).
Douglas, B.H.; Langford, HG. and McCaa, R.E.: Response of mineralocorticoid hypertensive animals to an angiotensin I converting enzyme inhibitor (40496). Proceedings of the Society for Experimental Biology and Medicine 161: 86–87 (1979).
Duchin, K.L. and Steinbacher, T.E.: Effects of Captopril (SQ 14, 225) on renal function in the dog. Kidney International 14: 693 (1978).
Dzau, V.J.; Colucci, W.S.; Williams, G.H.; Curfman, G.; Meggs, L. and Hollenberg, N.K.: Sustained effectiveness of converting-enzyme inhibition in patients with severe congestive heart failure. New England Journal of Medicine 302: 1373–1379 (1980).
Editorial: Captopril: benefits and risks in severe hypertension. Lancet 2: 129–130 (1980).
Eguchi, T.; Saito, I.; Nakamura, R., Yasui, T. and Saruta, T.: Effects of angiotensin I converting enzyme inhibitor (SQ 14225) on control of aldosterone. Acta Endocrinologica 94: 213–220 (1980).
Elijovich, F. and Krakoff, L.R.: Absolute sensitivity to angiotensin II and converting enzyme inhibition in glucocorticoid hypertension. Clinical Research 27: 592A (1979).
Elijovich, F. and Krakoff, L.R.: Captopril associated granulocytopenia in hypertension after renal transplantation. Lancet 1: 1927 (1980).
Fagard, R.; Amery, A.; Lijnen, P. and Reybrouck, T.: Haemodynamic effects of Captopril in hypertensive patients: comparison with saralasin. Clinical Science 57: 131S–134S (1979).
Fagard, R.; Amery, A.; Reybrouck, T.; Lijnen, P. and Billiet, L.: Acute and chronic systemic and pulmonary hemodynamic effects of angiotensin converting enzyme inhibition with Captopril in hypertensive patients. American Journal of Cardiology 46: 295–300 (1980a).
Fagard, R.; Amery, A.; Lijnen, P. and Staessen, J.: First dose effect of the oral angiotensin converting enzyme inhibitor Captopril. Archives Internationales de Pharmacodynamie et de Thérapie, Supplement (Symposium: Clinical Pharmacology of Antihypertensive Agents, 1980b).
Farrow, P.R. and Wilkinson, R.: Reversible renal failure during treatment with Captopril. British Medical Journal 1: 1680 (1979).
Favre, L.; Frazer, M.G. and Hollifield, J.W.: An orally active angiotensin I-converting enzyme inhibitor for therapy of hypertension. Clinical Research 26: 23A (1978a).
Favre, L.; Hollifield, J.W. and McKinstry, D.N.: Angiotensinconverting enzyme inhibition: A new medical therapy for hypertension? Journal of the Tennessee Medical Association 71: 201–202 (1978b).
Favre, L.; Frazer, M.; McKinstry, D.N. and Hollifield, J.W.: Chronic antihypertensive therapy with an oral converting-enzyme inhibitor (CEI). Circulation 58 (Part 2): 57 (1978c).
Ferguson, R.K.; Brunner, H.R.; Turini, G.A. and Gavras, H.: A specific orally active inhibitor of angiotensin-converting enzyme in man. Lancet 1: 775–778 (1977).
Ferguson, R.K.; Vlasses, P.H.; Koplin, J.R.; Shirinian, A.; Burke, J.F. and Alexander, J.C.: Captopril in severe treatment-resistant hypertension. American Heart Journal 99: 579–585 (1980).
Ferrone, R.A. and Antonaccio, M.J.: Prevention of the development of spontaneous hypertension in rats by Captopril (SQ 14, 225). European Journal of Clinical Pharmacology 60: 131–137 (1979).
Ferrone, R.A.; Antonaccio, M.J.; McGill, M.H.; Harns, D.N. and Goldenberg, H.: Role of Prostaglandins and βr-receptors in hemodynamic responses of spontaneously hypertensive rats to Captopril. Circulation 59 & 60(Suppl. 2): 200 (1979).
Fouad, F.M.; Ceimo, J.K.; Tarazi, R.C. and Bravo, E.L.: Oral converting enzyme inhibitor in resistant heart failure. Clinical Research 27: 673A (1979).
Freeman, R.H.; Davis, J.O.; Watkins, B.E.; Stephens, G.A. and De Forrest, J.M.: Effects of continuous converting enzyme blockade in renovascular hypertension in the rat. American Journal of Physiology 236: F21–F24 (1979).
Friedlander, D.H.: Captopril and Propranolol in mild and moderate essential hypertension; Preliminary report. New Zealand Medical Journal 90: 146–148 (1979)a).
Friedlander, D.H.: Comparison of Captopril with Propranolol in the treatment of essential hypertension. Medical Journal of Australia 2(No. 8, Suppl.): 30–32 (1979b).
Fujitani, K.; Mitsuda, H.; Eno, S.; Fukui, N.; Ishii, Y.; Furuta, Y.; Yoshida, M. and Miyoshi, A.: Effect of SQ 14,225 (Captopril) on hemodynamicus, plasma renin activity, plasma aldosterone concentration and plasma catecholamine in essential hypertension. Japanese Circulation Journal 43: 711–712 (1979).
Funke, P.T.; Ivashkiv, E.; Malley, M.F. and Cohen, A.I.: Gas chromatography/selected ion monitoring mass spectometric determination of Captopril in human blood. Analytical chemistry 52: 1086–1089 (1980).
Ganten, D. and Gross, F.: Interferences with the renin-angiotensin system and their effects on high blood pressure; in Gross (ed.) Antihypertensive Agents. Handbook of Experimental Pharmacology 39, pp.518–546 (Springer-Verlag, New York 1977).
Gavras, H.; Brunner, HR., Turini, G.A.; Kershaw, GR., Tifft, C.P.; Cuttelod, S.; Gavras, I.; Vukovich, R.A. and McKinstry, D.N.: Antihypertensive effect of the oral angiotensin converting-enzyme inhibitor SQ 14225 in man. New England Journal of Medicine 298: 991–995 (1978).
Greenberg, R.; Osman, G.H.; O’Keefe, E.H. and Antonaccio, M.J.: The effects of captopeil (SQ 14,225) on bradykinin-induced bronchoconstruction in the anesthetized guinea pig. European Journal of Pharmacology 57: 287–294 (1979).
Gross, F. and Liedtke, R.K. (ed): Pharmacology and clinical use of angiotensin I converting enzyme inhibitors (Gustav Fischer Verlag, Stuttgart and New York 1980).
Grossman, A.; Eckland, D.; Price, P. and Edwards, C.R.W.: Captopril: reversible renal failure with severe hyperkalaemia. Lancet 1: 712 (1980).
Haber, E.: Renin inhibitors. New England Journal of Medicine 298: 1023–1025 (1978).
Hall, J.E.; Guyton, A.C.; Coleman, T.G. and McCaa, R.E.: Long-term relationship between arterial pressure, urinary output, and renal hemodynamics after converting enzyme inhibition. (Abstract) 11th Annual American Society of Nephrology Meeting, New Orleans, November 19–21 (1978).
Hall, J.E.; Guyton, A.C.; Coleman, T.G. and Smith, M.J.: Role of angiotensin and aldosterone in control of arterial pressure and renal hemodynamics during chronic converting enzyme inhibition. Kidney International 16: 793 (1979).
Halperin, J.L.; Creager, M.A.; Faxon, D.P.; Gavras, H. and Ryan, T.J.: Chronic oral angiotensin inhibition for the treatment of refractory heart failure. Circulation 59 and 60(Suppl. 2): 39 (1979).
Hammond, J.J.; Kirkendall, W.M. and Jacks, V.L.: Experience with Captopril in the treatment of severe hypertension. Pharmacologist 21: 177 (1979).
Harris, D.N.; Heran, C.L.; Goldenberg, HJ.; High, J.P.; Laffen, R.J.; Rubin, B.; Antonaccio, M.J. and Goldberg, M.E.: Effects of SQ 14,225, an orally active inhibitor of angiotensin-converting enzyme on blood pressure, heart rate and plasma renin activity of conscious normotensive dogs. European Journal of Pharmacology 51: 345–349 (1978).
Hashimoto, K.; Ono, H. and Ohhara, N.: Acute antihypertensive effects with angiotensin I converting enzyme inhibitor, SQ 14,225. Presented at 52nd General Assembly, Japanese Pharmacological Society, Tokyo, March 26–29 (1979).
Heald, A.F. and Ita, C.E.: Distribution in rats of an inhibitor of angiotensin-converting enzyme, SQ 14,225, as studied by whole-body autoradiography and liquid scintillation counting. Pharmacologist 19: 129 (1977).
Heavey, DJ. and Reid, J.L.: The effect of SQ 14225 on baroreceptor reflex sensitivity in conscious normotensive rabbits. British Journal of Pharmacology 64: 389P–390P (1978).
Hermanovich, J.; Awan, N.A.; Skinner, P.; Amsterdam, E.A. and Mason, D.T.: Angiotensin-converting enzyme inhibition by oral Captopril related to nitroprusside in severe chronic congestive heart failure patients: equal preload benefit with dissimilarly enhanced pump output indicating Captopril resembles nitrate hemodynamic salutary effects. Clinical Research 27: 233A (1979).
Hollenberg, N.K.: Pharmacologic interruption of the reninangiotensin system. Annual Review of Pharmacology and Toxicology 19: 559–582 (1979).
Hoorntje, S.J.; Weening, J.J.; Kallenberg, C.G.M.; Prins, E.J.L. and Donker, Ab. J.M.: Serum-sickness-like syndrome with membranous glomerulopathy in patient on Captopril. Lancet 2: 1297 (1979a).
Hoorntje, S.J.; Prins, E.J.L. and Donker, Ab. J.M.: Captopril, angiotensin II, and sodium in blood-pressure regulation. Lancet 1: 1140 (1979b).
Hoorntje, S.J.; Weening, J.J.; The, T.H.; Kallenberg, C.G.M.; Donker, Ab. J.M. and Hoedemacker, P.J.: Immune-complex glomerulopathy in patients treated with Captopril. Lancet 1: 1212–1215 (1980).
Hornych, A.; Safar, M.; Gitelman, R.; Simon, A.; Bariéty, J. and Milliez, P.: The effect of Captopril (C) on plasma and urinary Prostaglandins (PG) in essential hypertension. World Conference on Clinical Pharmacology and Therapeutics, Abstract 0410, London, 3–9 August (1980).
Horovitz, Z.P.: Pharmacology and mechanism of action of inhibitors of the renin angiotensin system; in Gross and Liedtke (ed) Pharmacology and Clinical Use of Angiotensin I Converting Enzyme Inhibitors, p.9–16 (Gustav Fischer Verlag, Stuttgart and New York 1980).
Horovitz, Z.P.; Antonaccio, M.J.; Rubin, B. and Panasevich, R.E.: Influence of various antihypertensive agents on lifespan of renal hypertensive rats. British Journal of Clinical Pharmacology 7(Suppl. 2): 243S–248S (1979).
Huang, C.M.; Saloman, J.; Molteni, A.; Quintanilla, A. and del Greco, F.: Antihypertensive effect of Captopril and Propranolol. Clin. Pharmacol. Therapeut. 27: 258 (1980).
Hutchinson, J.S.; Mendelsohn, F.A.O. and Doyle, A.E.: Hypertensive action of Captopril and saralasin in intact and anephric spontaneously hypertensive rats. Hypertension 2: 119–124 (1980a).
Hutchinson, J.S.; Mendelsohn, F.A.O. and Doyle, A.E.: Blood pressure responses of conscious normotensive and spontaneously hypertensive rats to intracerebroventricular and peripheral administration of the angiotensin converting enzyme inhibitor, Captopril. Hypertension 2: 546–550 (1980b).
Hutchinson, J.S.; Mendelsohn, F.A.O.; Doyle, A.E. and Dufty, S.: Hypotensive activity of an orally active converting enzyme inhibitor in spontaneously hypertensive rats. Clinical and Experimental Pharmacology and Physiology 6: 676 (1979).
Imai, K.; Hashimoto, K.; Seki, T.; Yamaguchi, K.; Ohtaki, T.; Hayashi, Y. and Hashimoto, K.: Hematological alterations induced by Captopril (1-D-3-mercapto-2-methyl-1-oxopropyl-L-proline) in rats and dogs. Presented at the 6th Meeting Japanese Society of Toxicological Science, Osaka, June 1 (1979).
Imura, H.; Kono, T. et al.: Clinical application of angiotensin I converting enzyme inhibitor, SQ 14,225. Presented before the 52nd General Assembly, Japan Endocrine Society, Kyoto, June 7–9 (1979).
Jandhyala, B.S.; Naniwada, P.; Buckley, J.P. and Lokhandwale, M.F.: Studies on the mechanism of the hypotensive action of SQ-14225, an angiotensin-converting enzyme inhibitor in anesthetized dogs. Research Communications in Chemical Pathology and Pharmacology 25: 429–446 (1979).
Jandhyala, B.S.; Washington, G.F. and Lokhandwale, M.F.: Influence of inhibition of angiotensin I converting enzyme with SQ-14225 on the arterial blood pressure of mongrel dogs. Research Communications in Chemical Pathology and Pharmacology 22: 257–265 (1978).
Jenkins, A.C. and McKinstry, D.N.: Review of clinical studies of hypertensive patients treated with Captopril. Medical Journal of Australia 2(No. 8, Suppl.): 32–37 (1979).
Johns, D.W.; Baker, K.M.; Ayers, C.R.; Carey, R.M. and Peach, M.J.: Dilation of forearm vasculature following angiotensin converting enzyme inhibition by Captopril (SQ 14225) in severe hypertension. Circulation 59 & 60(Suppl. 2): 227 (1979).
Johns, D.W.; Baker, K.M.; Ayers, C.R.; Vaughan, E.D.; Carey, RM., Peach, M.J., Yancey, M.R.; Ortt, E.M. and Williams, S.C.: Acute and chronic effect of Captopril in hypertensive patients. Hypertension 2: 567–575 (1980).
Johnston, C.I.; McGrath, B.P.; Millar, J.A. and Matthews, P.G.: Long-term effects of Captopril (SQ 14225) on blood pressure and hormone levels in essential hypertension. Lancet 2: 493–495 (1979a).
Johnston, C.I.; McGrath, B.P. and Matthews, P.G.: Comparison of the hormonal effects of Captopril (SQ 14225) and hydrochlorothiazide in the treatment of essential hypertension. Medical Journal of Australia 2(No. 8, Suppl.): 17–22 (1979b).
Jones, D.R.; Butt, T.J. and Wallis, AT.: The effects of Captopril on the renal circulation of the rat. Medical Journal of Australia 2(No. 8, Suppl.): 11–12 (1979).
Karlberg, B.E.; Ohman, K.P.; Nilsson, O.R. and Wettre, S.: Captopril lowers urinary kallikrein in hypertensive patients. Lancet 1: 150–151 (1980).
Katovich, M.J.; Barney, C.C.; Fregly, M.J. and McCaa, RE.: Effect of an angiotensin converting enzyme inhibitor (SQ 14,-225) on βr-adrenergic and angiotensin-induced thirsts. European Journal of Pharmacology 56: 123–130 (1979).
Kawai, K.; Moeda, T.; Tanaka, K.; Kawamata, W.; Komai, T. and Shindo, H.: Studies on the metabolism of a new antihypertensive agent, SQ 14,225 (Captopril). II. Pharmacokinetics and metabolic fate of SQ 14,225-14C in dogs. 99th Annual Meeting of the Pharmaceutical Society of Japan, Sapporo, 28–30 August (1979).
Keim, HJ.; Bindel, G.; Distler, A.; Fleckenstein, P. and Cordes, U.: Long-term treatment of essential hypertension (EH) with the oral converting enzyme inhibitor SQ 14,225 [abstract]. Proceedings 6th Scientific meeting of the International Society of Hypertension, Goteborg, Sweden, June 11–13 (1979).
Keim, G.R.; Sibley, P.L.; Zaidi, I.H.; Keysser, C.H.; Kulesza, J.S.; Yoon, Y.H. and Zaki, F.G.: Effects of chronic inhibition of angiotensin-converting enzyme by Captopril in normotensive animals. Society of Toxicology Annual Conference, Washington D.C., March 13 (1980).
Kincaid-Smith, P.; Whitworth, J.A.; Walter, N.M.A. and Dowling, J.P.: Immune complex glomerulopathy and Captopril. Lancet 2: 37 (1980).
Koffer, H.; Vlasses, P.H.; Ferguson, R.K.; Koplin, J.R. and Nelson, L.A.: Long-term response to Captopril (cap) regimens in severe treatment-resistant hypertension (HBP). Clinical Research 28: 332A (1980).
Koike, H.; Ito, K.; Miyamoto, M. and Nishino, H.: Effects of chronic blockade of angiotensin converting enzyme with Captopril (CS-522) on hemodynamics and circulating blood volume in SHR. 60th Annual Meeting, Japanese Pharmacological Society, Tokyo Regional Meeting, Tokyo, June 18 (1979).
Koike, H.; Ito, K.; Miyamoto, M. and Nishino, H.: Effects of long-term blockade of angiotensin converting enzyme with Captopril (SQ 14,225) on hemodynamics and circulating blood volume in SHR. Hypertension 2: 299–303 (1980).
Kono, T.; Ikeda, F.; Oseko, F.; Imura, H. and Endo, J.: Effects of angiotensin-I converting enzyme inhibitor, SQ 14225, in normal men. Endocrinologica Japonica 26: 411–418 (1979)
Kripalani, K.J.; Singhvi, S.M.; Shaw, J.M.; Ross, J.J.; Meeker, F.S. and Migdalof, B.H.: The disposition of 35S-captopril (SQ 14,225) in mice. Pharmacologist 20: 213 (1978).
Kripalani, K.J.; McKinstry, D.N.; Singhvi, S.M.; Willard, D.A.; Vokovich, R.A. and Migdalof, B.M.: Disposition of Captopril in normal subjects. Clinical Pharmacology and Therapeutics 27: 636–641 (1980a).
Kripalani, K.J.; Meeker, F.S.; Dean, A.V.; McKinstry, D.N. and Migdalof, B.H.: Biotransformation of 14C-captopril in hypertensive patients and normal subjects. Federation Proceedings 39: 307 (1980b).
Laffan, R.J.; Goldberg, M.E.; High, J.P.; Schaeffer, T.R.; Waugh, M.H. and Rubin, B.: Antihypertensive activity in rats of SQ 14,225, an orally active inhibitor of angiotensin I-converting enzyme. Journal of Pharmacology and Experimental Therapeutics 204: 281–288 (1978).
Lai, F.M.; Tanikella, T.K.; Thibault, L. and Herzlinger, H.: Effects of Captopril on serum angiotensin converting enzyme activity and on blood pressure in the hypertensive rat. Pharmacologist 21: 178 (1979).
Laragh, JH.: The renin system in high blood pressure, from disbelief to reality: Converting-enzyme blockade for analysis and treatment. Progress in Cardiovascular Diseases 21: 159–166 (1978).
Laragh, J.H.; Case, D.B.; Atlas, S.A. and Sealey, J.E.: Captopril compared with other antirenin system agents in hypertensive patients: Its triphasic effects on blood pressure and its use to identify and treat the renin factor. Hypertension 2: 586–593 (1980).
Larochelle, P.; Genest, J.; Kuchel, O.; Boucher, R.; Gutkowska, Y. and McKinstry, D.: Effect of Captopril (SQ 14225) on blood pressure, plasma renin activity and angiotensin I converting enzyme activity. Canadian Medical Association Journal 121: 309–316 (1979).
Leslie, B.R.; Case, D.B.; Sullivan, J.F. and Vaughan, E.D.: Absence of blood-pressure lowering effect of Captopril in anephric patients. British Medical Journal 280: 1067 (1980).
Levenson, J.; Simon, A.; Temmar, M. and Safar, M.: Action antihypertensive du Captopril: étude hémodynamique. Nouvelle Presse Médicale 9: 617–619 (1980).
Levin, L. and Logan, K.: Response of malignant hypertension with refractory cardiac failure to Captopril. South African Medical Journal 58: 217–218 (1980).
Levine, T.B.; Franciosa, J.A. and Cohn, J.N.: Acute and long-term response to an oral converting-enzyme inhibitor, Captopril, in congestive heart failure. Circulation 62: 35–41 (1980).
Lijnen, P.; Fagard, R.; Staessen, J.; Verschueren, L.J. and Amery, A.: Dose response in Captopril therapy of hypertension. Clinical Pharmacology and Therapeutics 28: 310–315 (1980).
Lindner, A. and Cutler, R.E.: Acute renal failure (ARF) in the dog. Protection by angiotensin converting enzyme inhibitor (CEI). Kidney International 16: 785 (1979).
Lopez-Ovejero, J.A.; Saal, S.D.; D’Angelo, W.A.; Cheigh, J.S.; Stenzel, K.H. and Laragh, JH.: Reversal of vascular and renal crises of selerderma by oral angiotensin-converting-enzyme blockade. New England Journal of Medicine 300: 1417–1419 (1979).
Low, R.; Hermanovich, J.; Awan, N.A.; Stifter, W. and Mason, D.T.: Comparative cardiocirculatory actions of the oral angiotensin converting enzyme inhibitor Captopril to nitroprusside: disparate pump output with equal preload improvement in severe chronic congestive heart failure. Clinical Research 28: 192A (1980).
Loyke, H.F.: The effect of converting enzyme and angiotensin II blockade in chronic experimental hypertension. Proceedings 7th World Congress of Cardiology, p. 320, Tokyo, September (1978).
Luderer, J.R.; Schneck, D.W.; Demers, L.M.; McKinstry, D.N.; Vary, J.E. and Hayes, A.H.: The humoral effects of Captopril and furosemide in hypertensive patients. Clinical Pharmacology and Therapeutics 27: 268 (1980).
MacGregor, G.A.; Markandu, N.D. and Roulston, J.E.: Does the renin-angiotensin system maintain blood pressure in both hypertensive and normotensive subjects? A comparison of Propranolol, saralasin and Captopril. Clinical Science 57: 145S–148S (1979a).
MacGregor, G.A.; Markandu, N.D.; Roulston, J.E. and Jones, J.C.: Essential hypertension: effect of an oral inhibitor of angiotensin-converting enzyme. British Medical Journal 2: 1106–1109 (1979b).
Maeda, T.; Tanaka, K.; Kawameta, W.; Komai, T. and Shindo, H.: Studies on the metabolism of a new antihypertensive agent, SQ 14,225 (Captopril). I. In vitro studies on the binding to plasma protein and behaviour in blood. 99th Annual Meeting, Pharmaceutical Society of Japan, Sapporo, 28–30 August (1979).
Maitra, S.; Miyazaki, S.; Scicli, A.G. and Carretero, O.A.: Role of mineralocorticoid in the chronic antihypertensive effect of SQ 14,225. Circulation 59 & 60(Suppl. 2): 228 (1979).
Manin’t Veld, A.J.; Schicht, I.M.; Derkx, F.M.; de Bruyn, J.H.B. and Schalekamp, M.A.D.H.: Effects of an angiotensin-converting enzyme inhibitor (Captopril) on blood pressure in anephric subjects. British Medical Journal 1: 288–290 (1980).
Man in’t Veld, A.J.; Wenting, G.J. and Schalekamp, M.A.D.H.: Does Captopril lower blood pressure in anephric patients. British Medical Journal 2: 1110 (1979).
Mann, J.F.E.; Rascher, W.; Dietz, R.; Phillips, M.I.; Schomig, A. and Ganten, D.: Effects of the converting enzyme inhibitor SQ 14225 in spontaneously hypertensive rats. Clinical Research 27: 186A (1979).
Mann, J.F.E.; Rascher, W.; Dietz, R.; Schomig, A. and Ganten, D.: Effects of an orally active converting-enzyme inhibitor, SQ 14225, on pressor responses to angiotensin administered into the brain ventricles of spontaneously hypertensive rats. Clinical Science 56: 585–589 (1979).
Marin-Grez, M.; Bonner, G. and Gross, F.: Captopril, kallikrein and hypertension. Lancet 1: 1033 (1980).
Marks, E.S.; Bing, R.F.; Thurston, H. and Swales, J.D.: Vasodepressor property of the converting enzyme inhibitor Captopril (SQ 14225): the role of factors other than reninangiotensin blockade in the rat. Clinical Science 58: 1–6 (1980).
Maruyama, A.; Ogihara, T.; Naka, T.; Mikami, H.; Hata, T.; Nakamura, M.; Iwanaga, K. and Kumahara, Y.: Long-term effects of Captopril in hypertension. Clinical Pharmacology and Therapeutics 28: 316–323 (1980).
Mason, D.T.; Hermanovich, J.; Evensen, M. and Awan, N.A.: Oral Captopril in ambulatory management of severe congestive heart failure: sustained beneficial effects on ventricular function with 6 months therapy shown by cardiac catheterization, nuclear scintigraphy, echography, treadmill exercise and symptomatology. American Journal of Cardiology 45: 411 (1980).
Matthews, P.G. and Johnston, C.I.: Responses of the reninangiotensin system and kallikrein-kinin system to sodium and converting enzyme inhibitor (SQ 14,225); in Fujii, S. et al. (Eds) Kinins-II. Systemic Proteases and Cellular Function, pp.447–457 (Plenum Press, New York 1978).
Matthews, P.G. and Johnston, C.I.: Changes in endogenous circulating angiotensin and bradykinin after inhibition of converting enzyme (kininase II). Medical Journal of Australia 2(No. 8, Suppl.): 12–15 (1979).
McCaa, R.E.: Studies in vivo with angiotensin I converting enzyme (kininase II) inhibitors. Federation Proceedings 38: 2783–2787 (1979).
McCaa, R.E.: Specificity of converting enzyme inhibition; in Gross and Vogel (ed.) Enzymatic Release of Vasoactive Peptides, pp.383–399 (Raven Press, New York 1980).
McCaa, R.E.; Hall, J.E. and McCaa, CS.: The effects of angiotensin I-converting enzyme inhibitors on arterial blood pressure and urinary sodium excretion. Role of the renal reninangiotensin and kallikrein-kinin systems. Circulation Research 43(Suppl. 1): 32–39 (1978).
McCaa, R.E.; McCaa, C.S.; Bengis, R.G. and Guyton, A.C.: Role of aldosterone in experimental hypertension. Journal of Endocrinology 81: 69P–71P (1979a).
McCaa, CS.; Langford, H.G.; Cushman, W.C and McCaa, R.E.: Response of arterial blood pressure and aldosterone to long-term administration of Captopril in patients with severe, treatment-resistant accelerated hypertension. Clinical Science 57(Suppl. 5): 371S–373S (1979b).
McCredie, D.A. and Powell, H.R.: Use of a converting-enzyme inhibitor in severe hypertension of end-stage renal function. Australian and New Zealand Journal of Medicine 10: 123 (1980).
McKinstry, D.N.; Singhvi, S.M.; Kripalani, K.J.; Dreyfuss, J.; Willard, D.A. and Vukovich, R.A.: Disposition and cardiovascular-endocrine effects of an orally active angiotensin-converting enzyme inhibitor, SQ 14,225, in normal subjects. Clinical Pharmacology and Therapeutics 23: 121–122 (1978).
McKinstry, D.N., Willard, D.A. and Vukovich, R.A.: Antihypertensive and hormonal effects of the converting-enzyme inhibitor, Captopril, alone or combined with hydrochlorothiazide. Clinical Pharmacology and Therapeutics 25: 237 (1979).
McNeil, J.J.; Anderson, A.; Christophidis, N.; Mendelsohn, F.A.O.; Coghlan, J. and Louis, W.J.: Comparison of Captopril and hydrochlorothiazide in the treatment of moderate hypertension. Medical Journal of Australia 2(No. 8, Suppl.): 22–24 (1979a).
McNeil, J.J.; Anderson, A.; Christophidis, N.; Jarrott, B. and Louis, W.J.: Taste loss associated with oral Captopril treatment. British Medical Journal 2: 1555–1556 (1979b).
Meggs, L.G. and Hollenberg, N.K.: Converting enzyme inhibition and the kidney. Hypertension 2: 551–557 (1980).
Migdalof, B.H.; Singhvi, S.M. and Kripalani, K.J.: thin-layer radiochromatographic determination of Captopril (SQ 14,225) and its disulfidedimermetabolite in blood. Journal of Liquid Chromatography 3: 857–865 (1980a).
Migdalof, B.H.; Wong, K.K.; Law, S.J.; Kripalani, K.J. and Singhvi, S.M.: Evidence for dynamic interconversion of Captopril and its disulfide metabolites in vivo. Federation Proceedings 39: 307 (1980b).
Millar, J.A. and Johnston, C.I.: Sequential changes in circulating levels of angiotensin I and II, renin and bradykinin after Captopril. Medical Journal of Australia 2(Nop. 8, Suppl.): 15–17 (1979).
Mimran, A.; Brunner, H.R.; Turini, G.A.; Waeber, B. and Brunner, D.: Effect of Captopril on renal vascular tone in patients with essential hypertension. Clinical Science 57: 421S–423S (1979).
Moncada, S.; Mullane, K.M. and Vane, J.R.: Prostacylin-release by bradykinin in vivo. British Journal of Pharmacology 66: 96P–97P (1979).
Morganti, A.; Pickering, T.G.; Lopez-Ovejero, J. and Laragh, J.H.: Humoral effects of the oral converting-enzyme inhibitor SQ 14225 in hypertensive patients in supine and tilted positions. Clinical Science 57: 149S–152S (1979).
Morganti, A.; Pickering, T.G.; Lopez-Ovejero, J.A. and Laragh, J.H.: Endocrine and cardiovascular influences of converting enzyme inhibition with SQ 14225 in hypertensive patients in the supine position and during head-up tilt before and after sodium depletion. Journal of Clinical Endocrinology and Metabolism 50: 748–754 (1980).
Morton, J.J.; Brown, J.J.; Casels-Stenzel, J.; Lever, A.F.; Robertson, J.I.S. and Tree, N.: Changes in the blood levels of angiotensin I, II and III in dogs infused at various doses with the converting enzyme inhibitor, SQ 14225: effect of inhibition on blood pressure. Clinical Science 56: 4P (1979).
Morton, J.J.; Tree, M. and Casals-Stenzel, J.: The effect of Captopril on blood pressure and angiotensins I, II and III in sodium-depleted dogs: problems associated with the measurement of angiotensin II after inhibition of converting enzyme. Clinical Science 58: 445–450 (1980).
Muirhead, E.E.; Prewitt, R.L.; Brooks, B. and Brosius, W.L.: Antihypertensive action of the orally active converting enzyme inhibitor(SQ 14,225) in spontaneously hypertensive rats. Circulation Research 43(Suppl. 1): 53–59 (1978).
Murthy, V.S.; Waldron, T.S. and Goldberg, M.E.: Inhibition of aniotensin-converting enzyme by SQ 14,225 in anaesthetized dogs: haemodynamic and renal vascular effects (40004). Proceedings of the Society for Experimental Biology and Medicine 157: 121–124 (1978a).
Murthy, V.S.; Waldron, T.L. and Goldberg, M.E.: The mechanism of bradykinin potentiation after inhibition of angiotensin-converting enzyme by SQ 14,225 in conscious rabbits. Circulation Research 43(Suppl. 1): 40–45 (1978b).
Murthy, V.S.; Waldron, T.S.; Goldberg, M.E. and Vollmer, R.R.: Inhibition of angiotensin converting enzyme by SQ 14,225 in conscious rabbits. European Journal of Pharmacology 46: 207–212 (1977).
Nakano, T. and Taira, N.: Potentiation of the algogenic action of bradykinin by an inhibitor of angiotensin-I converting enzyme, Captopril (SQ -14,225). Japanese Journal of Pharmacology 29: 563–571 (1979).
Nicholls, M.G.; Espiner, E.A.; Ikram, H. and Maslowski, A.H.: Hyponatraemia in congestive heart failure during treatment with Captopril. British Medical Journal 281: 909 (1980).
Nishiyama, K.; Takeda, T.; Nakamura, Y.; Isii, M.; Matsuoka, H.; Goto, A.; Kimura, K.; Hirata, Y. and Murao, S.: The effect of angiotensin-converting enzyme inhibition on regional blood flow in salt-depleted and salt-loaded normotensive conscious rats. Japanese Heart Journal 20: 367–373 (1979).
Oberfield, S.E.; Case, D.B.; Levine, L.S.; Rapaport, R.; Rauh, W. and New, M.I.: Use of the oral angiotensin I-converting enzyme inhibitor (Captopril) in childhood malignant hypertension. Journal of Pediatrics 95: 641–644 (1979).
Ondtti, M.A.; Rubin, B. and Cushman, D.W.: Design of specific inhibitors of angiotensin-converting enzyme: New class of orally active antihypertensive agents. Science 196: 441–444 (1977).
Olsen, U.B. and Arrigoni-Martelli, E.: The effects of kininase II inhibition by SQ 14225 on kidney kallikrein-kinin and Prostaglandin systems in conscious dogs. European Journal of Pharmacology 54: 229–234 (1979).
O’Regan, S. and Robitaille, P.: Successful treatment of severe hypertension associated with chronic allograft rejection. Unpublished report, on file, Squibb (1980).
Parfrey, P.S.; Clement, M.; Vandenburg, M.J. and Wright, P: Captopril-induced pemphigus. British Medical Journal 281: 194 (1980).
Phelan, E.L. and Clarke, D.W.J.: Effect of Captopril on blood pressure and vascular resistance in normotensive and genetically hypertensive rats. Medical Journal of Australia 2(No. 8, Suppl.): 9–10 (1979).
Pipkin, F.B.; Turner, S.R. and Symonds, E.M.: Possible risk with Captopril in pregnancy: some animal data. Lancet 1: 1256 (1980).
Prins, E.J.L.; Hoorntje, S.J.; Weening, J.J. and Donker, Ab. J.M.: Nephrotic Syndrome in patient on Captopril. Lancet 2: 306–307 (1979).
Rommel, A.J.; Pierides, A.M. and Heald, A.: Captopril Elimination in chronic renal failure. Clinical Pharmacology and Therapeutics 27: 282 (1980).
Rosendorff, C.: Angiotensin converting enzyme inhibition in the treatment of esseantial hypertension. Proceedings 6th Scientific Meeting of the International Society of Hypertension, Goteborg, Sweden, June 11–13 (1979).
Rosendorff, C.; Milne, F.J.; Levy, H.; Ninin, D.T. and Lewin, J.R.: Nephrotic syndrome during Captopril therapy. South African Medical Journal 58: 172–173 (1980).
Rubin, B.; Laffan, R.J.; Kotier, D.G.; O’Keefe, E.H.; Demaio, D.A. and Goldberg, M.E. SQ 14,225 (D-3-mercapto-2-methylpropranoyl-L-proline), a novel orally active inhibitor of angiotensin-I converting enzyme. Journal of Pharmacology and Experimental Therapeutics 204: 271–280 (1978).
Saragoca, M.; Tarazi, R.C.; Bravo, E.L. and Fouad, F.M.: Contrast between acute and longer term responses to oral converting enzyme inhibitor (CEI). Clinical Research 27: 317A (1979).
Scholkens, B.A.; Steinbach, R. and Jung, W.: Intracerebroventricular injection of an angiotensin I converting enzyme inhibitor (SQ 14225) in animals with experimental hypertension. Naunyn-Schmeideberg’s Archives of Pharmacology 307 (Suppl.) R46 (1979).
Seedat, Y.K.: Comparison of Captopril with Propranolol in the treatment of mild and moderate essential hypertension. South African Medical Journal 56: 983–986 (1979a).
Seedat, Y.K.: Apthous ulcers of mouth from Captopril. Lancet 2: 1297–1298 (1979b).
Seedat, Y.K.: Nephrotic syndrome from Captopril. South African Medical Journal 57: 390 (1980).
Sen, S.; Tarazi, R.C. and Bumpus, F.M.: Effect of converting enzyme inhibitor (SQ 14,225) on myocardial hypertrophy in spontaneously hypertensive rats. Hypertension 2: 169–176 (1980).
Sharpe, D.N.: Comparison of Captopril (SQ 14225) with hydrochlorothiazide in the treatment of mild and moderate essential hypertension. Medical Journal of Australia 2(No. 8, Suppl.): 24–26 (1979).
Sharpe, D.N.; Coxon, R. and Long, B.: Converting enzyme inhibition in severe chronic heart failure: Acute haemodynamic effects and long term treatment. Manuscript submitted for publication (1980).
Sibley, P.L.; Keim, G.R.; Keysser, C.H.; Kulesza, J.S.; Miller, M.M. and Zaidi, I.H.: SQ 14,225, an orally active inhibitor of angiotensin-converting enzyme: acute and subacute toxicity in animals. Toxicology and Applied Pharmacology 45: 315 (1978).
Snyder, D.W.; Meyerson, N.G.; Harris, D.N. and Goldenberg, HJ.: The role of renin-angiotensin system in neurogenic hypertension in rats. Federation Proceedings 38: 1200 (1979).
Staessen, J.; Fagard, R.; Lijnen, P. and Amery, A.: Captopril and agranulocytosis. Lancet 1: 926–928 (1980).
Stamler, J.F.; Brody, M.J. and Phillips, M.I.: The central and peripheral effects of Captopril (SQ 14225) on the arterial pressure of the spontaneously hypertensive rat. Brain Research 186: 499–503 (1980).
Sullivan, J.M.; Ginsburg, B.A.; Ratts, T.E.; Johnson, J.G.; Barton, B.R.; Kraus, D.H.; McKinstry, D.N. and Muirhead, E.E.: Hemodynamic and antihypertensive effects of Captopril, an orally active angiotensin converting enzyme inhibitor. Hypertension 1: 397–401 (1979).
Swales, J.D.: Renin-angiotensin system in hypertension. Pharmacology and Therapeutics 7: 173–201 (1979).
Swales, J.D.; Thurston, H. and Bing, R.F.: Reversal of experimental hypertension by oral renin-angiotensin blockade and by surgical correction. Proceedings 5th Scientific Meeting of the International Society of Hypertension, Paris, June 12–14 (1978). Clinical Science and Molecular Medicine (Supplement), p. 265 (1978).
Swartz, S.L.; Williams, G.H.; Moore, T.J.; Dluhy, R.G. and Hollenberg, N.K.: Primacy of the renin-angiotensin system in mediating aldosterone’s response to Na restriction. Clinical Research 27: 318A (1979).
Swartz, S.L.; Williams, G.H.; Hollenberg, N.K.; Levine, L.; Dluhy, R.G. and Moore, T.J.: Captopril-induced Changes in Prostaglandin Production. Journal of Clinical Investigation 65: 1257–1264 (1980).
Sweet, C.S. and Columbo, J.M.: Cardiovascular properties of anti-hypertensive drugs in a model of severe renal hypertension. Journal of Pharmacological Methods 2: 223–239 (1979).
Tarazi, R.C.; Fouad, F.M.; Ceimo, J.K. and Bravo, E.L.: Renin, aldosterone and cardiac decompensation: studies with an oral converting enzyme inhibitor in heart failure. American Journal of Cardiology 44: 1013–1018 (1979).
Tarazi, R.C.; Bravo, E.L.; Fouad, F.M.; Omvik, P. and Cody, R.J.: Hemodynamic and volume changes associated with Captopril. Hypertension 2: 576–585 (1980).
Thurston, H.; Bing, R.F. and Swales, J.D.: Blood pressure maintenance and chronic renovascular hypertension. Proceedings 6th Scientific Meeting of the International Society of Hypertension, Goteborg, Sweden, June 11–13 (1979).
Tobia, A. and Giardino, E.: Captopril-induced renal vasodilation in pentobarbital anesthetized dogs. Federation Proceedings 39: 1189 (1980).
Turini, G.A.; Brunner, H.R.; Waeber, B.; Curtet, N. and Gavras, H.: Long term cardiac responses of hypertensive patients treated by an inhibitor of angiotensin converting enzyme. Clinical Research 27: 319A (1979a).
Turini, G.A.; Gribic, M.; Brunner, H.R.; Waeber, B. and Gavras, H.: Improvement of chronic congestive heart-failure by oral Captopril. Lancet 1: 1213–1215 (1979b).
Unger, Th.; Rockhold, R.W.; Bonner, G.; Vecsei, P. and Ganten, D.: Long-term oral administration of converting enzyme inhibitor (SQ 14225) in spontaneously hypertensive rats. Naunyn-Schmeideberg’s Archives of Pharmacology 307 (Suppl.): R46 (1979).
van Brummelen, P.; Willemze, R.; Tan, W.D. and Thompson, J.: Captopril-associated agranulocytosis. Lancet 1: 150 (1980).
Vaughan, E.D.; Carey, R.M.; Ayers, C.R. and Peach, M.J.: Hemodialysis-resistant hypertension: control with an orally active inhibitor of angiotensin-converting enzyme. Journal of Clinical Endocrinology and metabolism 48: 869–871 (1979).
Vecsei, P.; Hackenthal, E. and Ganten, D.: The renin-angiotensin-aldosterone system. Past, present and future. Klinische Wochenschrift 56(Suppl. 1): 5–21 (1978).
Vinci J.M.; Zusman, R.M.; Izzo, J.L.; Bowden, RE.; Horwitz, D.; Pisano, J.J. and Keiser, H.R.: Human urinary and plasma kinins. Relationship to sodium-retaining steroids and plasma renin activity. Circulation Research 44: 228–237 (1979).
Vlasses, P.H. and Ferguson, R.K.: Temporary ageusia related to Captopril. Lancet 2: 526 (1979).
Vlasses, P.H.; Koplin, J.R.; Burke, J.F. and Ferguson, R.K.: Patterns of blood pressure (BP) response to Captopril (CAP) in treatment-resistant hypertension, Clinical Research 27: 319A (1979).
Vollmer, R.R. and Boccagno, J.A.: Central cardiovascular effects of SQ 14.225, an angiotensin-converting enzyme inhibitor in chloralose-anaesthetized cats. European Journal of Pharmacology 45: 117–125 (1977).
Vollmer, R.R.; Bocagno, J.A.; Harris, D.N. and Murthy, V.S.: Hypotension induced by inhibition of angiotensin-converting enzyme in pentobarbital-anesthetized dogs. European Journal of Pharmacology 51: 39–45 (1978).
Waeber, B.; Guignard, J.P.; Brunner, H.R.; Turini, G.A. and Gavras, H.: Treatment of severe renal hypertension in a child with an inhibitor of the angiotensin converting enzyme (SQ 14,225). Helvetica Paediatrica Acta A1978(S40): 10–11 (1978a).
Waeber, B.; Gavras, H.; Brunner, H.R.; Chappius, Ph. and Turini, G.A.: Traitement chronique de l’hypertension arterielle par un inhibiteur de l’enzyme de conversion de l’angiotensine. Schweizerische Medizinische Wochenschrift 108: 1981–1983 (1978b).
Waeber, B.; Brunner, H.R.; Brunner, D.B.; Curtet, A-L.; Turini, G.A. and Gavras, H.: Discrepancy between antihypertensive effect and angiotensin converting enzyme inhibition by Captopril. Hypertension 2: 236–242 (1980).
Wagner, L.A.; Wagner, L.B. and Clarke, D.E.: Mechanism of antihypertensive action of SQ 14225 in rats. Federation Proceedings 38: 738 (1979).
Waldron, T.L. and Murthy, V.S.: Hemodynamic effects of SQ 14,225, an orally effective angiotensin converting enzyme (ACE) inhibitor, in dogs. Federation Proceedings 37: 718 (1978).
Waldron, T.L.; Murthy, V.S. and Goldberg, M.E.: SQ 14,225, a new orally effective angiotensin converting enzyme inhibitor. Hemodynamic and renal effects in dogs. Pharmacologist 19: 213 (1977).
Warren, S.E.; Cohen, I.M.; O’Connor, D.T.; Cervenka, J. and Stone, R.A.: Heterogeneity of renal hemodynamic response to Captopril (C). Kidney International 16: 908 (1979).
Watanabe, T.X. and Sokabe, H.: Acute vasodepressor effect of D-3-Mercapto-2-Methylpropanoyl-L-Proline (SQ 14,225) in the stroke-prone substrain of spontaneously hypertensive rats (SHRSP). Japanese Journal of Pharmacology. 29: 133–135 (1979).
Watkins, B.E.; Davis, J.O.; Freeman, R.H.; Stephens, G.A. and DeForrest, J.M.: Effects of the oral converting enzyme inhibitor (SQ 14225) on one-kidney hypertension in the dog (40030). Proceedings of the Society for Experimental Biology and medicine 157: 245–249 (1978).
Weed, W.C.; Vaughan, E.D. and Peach, M.J.: Prolongation of the saralasin responsive state of two-kidney, one clip Goldblatt hypertension in the rat by the orally administered converting enzyme inhibitor Captopril (SQ 14,225). Hypertension 1: 8–12 (1979).
Weinberger, M.H.: Angiotensin converting enzyme inhibition (ACEI) in treatment of resistant hypertension. Clinical Pharmacology and Therapeutics 27: 293 (1980).
White, N.J.; Yahaya, H.; Rajagopalan, B. and Ledingham, J.G.G.: Captopril and frusemide in severe drug resistant hypertension. Lancet 2: 108–110 (1980).
Whitman, H.H.; Case, D.B.; Botstein, G.; Maricq, H.; LeRoy, E.C.; Laragh, J.H. and Christian, C.L.: Variable response to oral converting enzyme blockade in hypertensive scleroderma patients. Arthritis and Rheumatism 23: 762–763 (1980).
Whitworth, J.A.; Walter, N.M.A. and Kincaid-Smith, P.: Clinical trial of an orally administered converting enzyme inhibitor (Captopril). Medical Journal of Australia 2(No. 8, Suppl.): 27–30 (1979).
Wilkin, J.K.; Hammond, J.J. and Kirkendall, W.M.: The captopril-induced eruption. Archives of Dermatology 116: 902–905 (1980).
Wong, K.K. and Dreyfuss, J.: The in vitro metabolism of 35S-captopril (SQ 14,225), an antihypertensive agent. Pharmacologist 20: 213 (1978).
Woodhouse, K.; Farrow, P.R. and Wilkinson, R.: Reversible renal failure during treatment with Captopril. British Medical Journal 2: 1146–1147 (1979).
Woods, D.M. and Shimizu, A.: Scleroderma renal crisis: use of angiotensin-converting-enzyme in treatment. Unpublished report, on file, Squibb (1980).
Zappacosta, A.R.; Vlasses, P.H. and Fergusson, R.K: Captopril in refractory malignant hypertension. Drug Intelligence and Clinical Pharmacy 14: 373–374 (1980).
Zawada, E.T.; Clements, P.J.; Furst, D.A.; Bloomer, H.A.; Paulus, H.E. and Maxwell, M.H.: Clinical course of patients with scleroderma renal crisis (src) treated with Captopril (c). Kidney International 16: 140A (1979).
Zweifler, A.J.; Julius, S. and Nicholls, M.G.: Efficacy of an oral angiotensin converting enzyme inhibitor (Captopril) in severe hypertension. Clinical Research 27: 320A (1979).
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Various sections of the manuscript reviewed by: A.B. Atkinson, Medical Research Council Blood Pressure Unit, Western Infirmary, Glasgow, Scotland; SA. Atlas, Hypertension Center, New York Hospital-Cornell Medical Center, New York, USA; E.L. Bravo, Cleveland Clinic, The Clinic Center, Cleveland, Ohio, USA; H.R. Brunner, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; J. Chalmers, Department of Medicine, Flinders Medical Centre, Bedford Park, South Australia; H.P. Gavras, Hypertension Section, Boston City Hospital. Boston, USA; F. Grass, Department of Pharmacology, University of Heidelberg, Heidelberg, Germany; C.I. Johnston, Department of Medicine, Monash University, Melbourne, Australia; N.M. Kaplan, Department of Internal Medicine, University of Texas Health Science Center at Dallas, Dallas, Texas, USA; R.E. McCaa, University of Mississippi Medical Center, Jackson, Mississippi, USA; FA.O. Mendelsohn, Department of Medicine, Austin Hospital, University of Melbourne, Heidelberg, Victoria, Australia; M. Maser, Davis Avenue Medical Center, White Plains, New York, USA; J.I.S. Robertson. Medical Research Council Blood Pressure Unit, Western Infirmary, Glasgow, Scotland; N. Sharpe, Department of Medicine, University of Auckland, Auckland, New Zealand; F.O. Simpson, Wellcome Medical Research Institute, Dunedin, New Zealand; J.D. Swales, Department of Medicine, University of Leicester, Leicester Royal Infirmary, Leicester, England; J.A. Whitworth, Department of Nephrology, Royal Melbourne Hospital, Melbourne, Australia.
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Heel, R.C., Brogden, R.N., Speight, T.M. et al. Captopril: A Preliminary Review of its Pharmacological Properties and Therapeutic Efficacy. Drugs 20, 409–452 (1980). https://doi.org/10.2165/00003495-198020060-00001
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DOI: https://doi.org/10.2165/00003495-198020060-00001