Summary
Enalaprilic acid (MK 422), the active metabolite of enalapril, has recently become available for intravenous administration. In order to establish the proper dose for rapid blood pressure reduction, 9 patients with moderate to severe essential hypertension on a constant sodium intake of 100 mmol/24 h were studied. They received four single doses of MK 422 according to an up-and-down titration schedule. Doses between 5 and 80 mg resulted in effective blood pressure reduction with an onset of action of about 10 minutes. Within this dose range the response was flat. No symptomatic hypotension was observed. The fall in blood pressure was less pronounced in patients with low initial plasma renin activity (PRA). Accordingly, a study was done to show whether the blood pressure response could be augmented by preceding stimulation of PRA by injection of 40 mg furosemide 15 minutes before the administration of MK 422. PRA increased after furosemide, but the blood pressure response to MK 422 was not augmented.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Brunner HR, Turini GA, Waeber B, Gavras H (1981) Clinical pharmacological studies with captopril. In: Horovitz ZP (ed) Angiotensin converting enzyme inhibitors, mechanisms of action and clinical implications. Urban & Schwarzenberg, Baltimore Munich, pp 351–368
Ferguson RK, Vlasses PH, Swanson BN, Mojaverian P, Hichens M, Irvin JD, Huber PH (1981) Effects of enalapril, a new converting enzyme inhibitor in hypertension. Clin Pharmacol Ther 32: 48–53
Gross DM, Sweet CS, Ulm EH et al. (1981) Effect of N-[(S)-1-carboxy-3-phenyl propyl]-L-ala-L-pro and its ethyl ester MK 421) on angiotensin converting enzyme in vitro and angiotensin I pressor responses in vitro. J Pharmacol Exp Ther 216: 552–557
Case DB, Wallace JM, Keim HJ, Weber MA, Sealey J, Laragh JH (1977) Possible role of renin in hypertension as suggested by renin-sodium profiling and inhibition of converting enzyme. N Engl J Med 296: 641–646
Hesse B, Nielsen I, Lund-Jacobsen H (1975) The early effects of intravenous furosemide on central haemodynamics, venous tone and plasma renin activity. Clin Sci 49: 551–555
Freedlander AE, Fyrquist F, Hollemans HJG (1974) In: Jaffe BM, Behrmann HR (eds) Methods of hormone radioimmuno assay. Academic Press New York London
Pratt JJ, Boonman R, Woldring MG, Donker AJM (1978) Special problems in radioimmuno-assay of plasma aldosterone without prior extraction and purification. Clin Chim Acta 84: 329–337
Gavras H, Waeber B, Gavras I, Biollaz J, Brunner HR, Davies RO (1981) Antihypertensive effect of the new oral angiotensin converting enzyme inhibitor “MK-421”. Lancet 2: 543–547
Fouad FM, Tarazi RC, Bravo EL, Textor SC (1984) Hemodynamic and antihypertensive effects of the new oral angiotensin-converting-enzyme inhibitor MK-421 (Enalapril). Hypertension 6: 167–174
Vlasses PH, Rotmensch HH, Swanson BN et al. (1983) comparative antihypertensive effects of enalapril maleate and hydrochlorothiazide, alone and in combination. J Clin Pharmacol 23: 227–233
Kelly RA, Wilcox CS, Mitch WE et al. (1983) Response of the kidney to furosemide. II. Effect of captopril on sodium balance. Kidney Int 24: 233–239
Vander AJ, Carlson J (1969) Mechanisms of the effects of furosemide on renin secretion in anesthetized dogs. Circ Res 25: 145–152
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Navis, G.J., de Jong, P.E., Donker, A.J.M. et al. Blood pressure response to enalaprilic acid in essential hypertension: Dose-response and effect of pre-treatment with furosemide. Eur J Clin Pharmacol 29, 9–15 (1985). https://doi.org/10.1007/BF00547361
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00547361