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Effect of captopril and hydrochlorothiazide on the response to pressor agents in hypertensives

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Summary

The effect on arterial pressure of incremental doses of norepinephrine (2 to 10 µg/min) and angiotensin II (50 to 800 ng/min) administered over 10 min periods was studied in sodium-replete hypertensive patients after crossover oral treatments with placebo, captopril 50 mg in a single dose, captopril 50 mg three times daily for one week and hydrochlorothiazide 50 mg daily for a week. Neither captopril nor hydrochlorothiazide affected the dose response to infusions of angiotensin II. In comparison to placebo responses, however, both single and multiple-dose captopril therapy, and hydrochlorothiazide attenuated the pressor responses to infusions of norepinephrine. Captopril significantly depressed angiotensin converting enzyme activity from predose levels and angiotensin II infusions significantly elevated plasma aldosterone concentrations. These results confirm findings reported for single dose captopril in normotensive volunteers and indicate that attenuation of the vascular responsiveness to sympathetic stimulation may contribute to the antihypertensive effects of captopril and hydrochlorothiazide therapy.

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References

  1. Abe K, Itoh T, Imai Y, Sato M, Haruyama T, Sakurai Y, Goto T, Otsuka Y, Yoshinaga K (1980) Implication of endogenous prostaglandin system in the antihypertensive effect of captopril, SQ 14, 225, in low renin hypertension. Jpn Circ J 44: 422–425

    PubMed  CAS  Google Scholar 

  2. Antonaccio MJ, Kerwin L (1981) Pre- and post-junctional inhibition of vascular sympathetic function by captopril in SHR. Hypertension 3 [Suppl]: I-54–I-62

    CAS  Google Scholar 

  3. Beavers WR, Blackmore WP (1958) Effect of chlorothiazide on vascular reactivity. Proc Exp Biol Med 98: 133–135

    CAS  Google Scholar 

  4. Boura ALA, Hi S-CG, Rechtman MP, Walters WAW (1982) Captopril inhibits pressor responses to peripheral sympathetic nerve activation in cats and rats. Clin Exp Pharmacol Physiol 7 [Suppl]: 123–128

    CAS  Google Scholar 

  5. Bravo EL, Tarazi RC (1979) Converting enzyme inhibition with an orally active compound in hypertensive man. Hypertension 1: 39–46

    PubMed  CAS  Google Scholar 

  6. Clough DP, Hatton R, Keddie JR, Collis MG (1982) Hypotensive action of captopril in spontaneously hypertensive and normotensive rats. Interference with neurogenic vasoconstriction. Hypertension 4: 764–772

    PubMed  CAS  Google Scholar 

  7. Dawson-Hughes BF, Moore TJ, Dluhy RG, Hollenberg MK, Williams GH (1981) Plasma angiotensin II regulates vascular but not adrenal responsiveness to restriction of sodium intake in normal man. Clin Sci 61: 527–534

    PubMed  CAS  Google Scholar 

  8. Fagard RH, Amery A, Lijnen PJ, Reybrouck TM (1980) Comparative study of an angiotensin II — analog and a converting enzyme inhibitor. Kidney Int 17: 647–653

    Article  PubMed  CAS  Google Scholar 

  9. Feisal KA, Eckstein JW, Horsley AW, Keasling HH (1961) Effects of chlorothiazide on forearm vascular responses to norepinephrine. J Appl Physiol 16: 549–552

    PubMed  CAS  Google Scholar 

  10. Ferguson RK, Turini GA, Brunner HR, Gavras H (1977) A specific orally active inhibitor of angiotensin converting enzyme in man. Lancet 1: 775–778

    Article  PubMed  CAS  Google Scholar 

  11. Ferris TF (1982) The kidney in hypertension. Arch Int Med 142: 1889–1895

    Article  CAS  Google Scholar 

  12. Freis ED, Wanko A, Schnaper HR, Frohlich ED (1960) Mechanism of the altered blood pressure responsiveness produced by chlorothiazide. J Clin Invest 39: 1277–1281

    Article  PubMed  CAS  Google Scholar 

  13. Grimm M, Weidmann P, Meier A, Keusch G, Ziegler W, Gluck Z, Beretta-Piccola C (1981) Correction of altered noradrenaline reactivity in essential hypertension by indapamide. Br Heart J 46: 404–409

    Article  PubMed  CAS  Google Scholar 

  14. Haber E, Koerner D, Page LB, Kliman B, Purnode A (1969) Application of a radioimmunoassay for angiotensin I to the physiologic measurement of plasma renin activity in normal human subjects. J Clin Endocrinol 29: 1349–1355

    CAS  Google Scholar 

  15. Hollenberg NK, Chenitz WR, Adams DF, Williams GH (1974) Reciprocal influence of salt intake on adrenal glomerulosa and renal vascular responses to angiotensin II in normal man. J Clin Invest 54: 34–42

    Article  PubMed  CAS  Google Scholar 

  16. Imai Y, Abe K, Seino M, Haruyama T, Tajima J, Sato M, Goto T, Hiwatari M, Kasai Y, Yoshinaga K, Sekino H (1982) Attenuation of pressor responses to norepinephrine and pitressin and potentiation of pressor response to angiotensin II by captopril in human subjects. Hypertension 4: 444–451

    PubMed  CAS  Google Scholar 

  17. Ichikawa S, Johnson JA, Fowler WL Jr, Payne CG, Kurz K, Keitzner WF (1978) Pressor responses to norepinephrine in rabbits with 3-day and 30-day renal artery stenosis: The role of angiotension II. Circ Res 43: 437–446

    PubMed  CAS  Google Scholar 

  18. Lake CR, Ziegler MG, Coleman MD, Kopin IJ (1979) Sustained sympathetic hyperactivity in hydrochlorothiazide-treated hypertensives. Clin Pharmacol Ther 1979; 26: 428–432

    CAS  Google Scholar 

  19. Lijnen P, Staessen J, Fagard R, Amery A (1982) Increase in plasma aldosterone during prolonged captopril treatment. Am J Cardiol 49: 1561

    Article  PubMed  CAS  Google Scholar 

  20. Ogihara T (1977) A non-chromatographic non-extraction radioimmunoassay for serum aldosterone. J Clin Endo Metab 45: 726

    CAS  Google Scholar 

  21. Shoback DM, Williams GH, Hollenberg NK, Davies RO, Moore TJ, Dluhy RG (1983) Endogenous angiotensin II as a determinant of sodium-modulated changes in tissue responsiveness to angiotensin II in normal man. J Clin Endocrinol Metal 57: 764–770

    Article  CAS  Google Scholar 

  22. Spertini F, Brunner HR, Waeber B, Gavras H (1981) The opposing effects of chronic angiotensin-converting enzyme blockade by captopril on the responses to exogenous angiotensin II and casopressin vs. norepinephrine in rats. Circ Res 48: 612–618

    PubMed  CAS  Google Scholar 

  23. Swanson BN, Hichens M, Mojaverian P, Ferguson RK, Vlasses PH, Dudash M (1981) Angiotensin converting enzyme activity in human serum: relationship to enzyme inhibitor in vivo and in vitro. Res Commun Chem Pathol Pharmacol 33: 525–536

    PubMed  CAS  Google Scholar 

  24. Vlasses PH, Rotmensch HH, Swanson BN, Mojaverian P, Ferguson RK (1982) Low dose captopril in mild to moderate hypertension unresponsive to diuretic treatment. Arch Intern Med 142: 1098–1101

    Article  PubMed  CAS  Google Scholar 

  25. Weidman P, Grimm M, Meier A, Gluck Z, Keusch G, Minder I, Beretta-Piccola C (1980) Pathogenic and therapeutic significance of cardiovascular pressor reactivity as related to plasma catecholamines in borderline and established essential hypertension. Clin Exp Hypertens 2: 427–449

    Article  Google Scholar 

  26. Weinberger MH, Ramsdell JW, Rosner DR, Geddes JJL (1972) Effect of chlorothiazide and sodium on vascular responsiveness to angiotensin II. Am J Physiol 223: 1049–1052

    PubMed  CAS  Google Scholar 

  27. Zoster TT, Hart F, Radde IC (1970) Mechanism of antihypertensive action of prolonged administration of hydrochlorothiazide in rabbit and dog. Circ Res 27: 717–725

    Google Scholar 

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Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA

    R. J. Fruncillo, H. H. Rotmensch, P. H. Vlasses, J. R. Koplin, B. N. Swanson & R. K. Ferguson

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  1. R. J. Fruncillo
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  2. H. H. Rotmensch
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  3. P. H. Vlasses
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  4. J. R. Koplin
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  5. B. N. Swanson
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  6. R. K. Ferguson
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Recipient of a Charles E. Culpeper Foundation Research Fellowship

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Fruncillo, R.J., Rotmensch, H.H., Vlasses, P.H. et al. Effect of captopril and hydrochlorothiazide on the response to pressor agents in hypertensives. Eur J Clin Pharmacol 28, 5–9 (1985). https://doi.org/10.1007/BF00635700

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  • DOI: https://doi.org/10.1007/BF00635700

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