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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1981 May;11(5):461–467. doi: 10.1111/j.1365-2125.1981.tb01151.x

Effect of a new angiotensin converting enzyme inhibitor MK 421 and its lysine analogue on the components of the renin system in healthy subjects.

D B Brunner, G Desponds, J Biollaz, I Keller, F Ferber, H Gavras, H R Brunner, J L Schelling
PMCID: PMC1401601  PMID: 6268131

Abstract

1 MK 421 and its lysine analogue are two new inhibitors of angiotensin converting enzyme. Ten mg of both compounds were each given p.o. to 12 normotensive volunteers to determine their effect on the various components of the renin angiotensin aldosterone system. 2 Plasma converting enzyme activity decreased to very low levels within 3 to 4 h to recover only slowly over the next 72 h. Plasma angiotensin II and aldosterone also fell but returned to baseline within 24 h, whereas plasma renin activity rose reflecting the low angiotensin II levels. 3 There was a close correlation between both angiotensin II and aldosterone levels and the logarithm of plasma converting enzyme activity demonstrating that angiotensin II and aldosterone fell only when converting enzyme activity was reduced to very low levels. 4 Mean hourly urinary sodium excretion increased markedly 6 to 10 h post-drug, while blood pressure decreased slightly. Both drugs were well tolerated. 5 Thus 10 mg of MK 421 or its lysine analogue given orally are effective and long acting angiotensin converting enzyme inhibitors.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brunner H. R., Gavras H., Waeber B., Kershaw G. R., Turini G. A., Vukovich R. A., McKinstry D. N., Gavras I. Oral angiotensin-converting enzyme inhibitor in long-term treatment of hypertensive patients. Ann Intern Med. 1979 Jan;90(1):19–23. doi: 10.7326/0003-4819-90-1-19. [DOI] [PubMed] [Google Scholar]
  2. Case D. B., Atlas S. A., Laragh J. H., Sealey J. E., Sullivan P. A., 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. Prog Cardiovasc Dis. 1978 Nov-Dec;21(3):195–206. doi: 10.1016/0033-0620(78)90025-7. [DOI] [PubMed] [Google Scholar]
  3. Davis R., Ribner H. S., Keung E., Sonnenblick E. H., LeJemtel T. H. Treatment of chronic congestive heart failure with captopril, an oral inhibitor of angiotensin-converting enzyme. N Engl J Med. 1979 Jul 19;301(3):117–121. doi: 10.1056/NEJM197907193010301. [DOI] [PubMed] [Google Scholar]
  4. Düsterdieck G., McElwee G. Estimation of angiotensin II concentration in human plasma by radioimmunoassay. Some applications to physiological and clinical states. Eur J Clin Invest. 1971 Nov;2(1):32–38. doi: 10.1111/j.1365-2362.1971.tb00565.x. [DOI] [PubMed] [Google Scholar]
  5. Ferguson R. K., Turini G. A., Brunner H. R., Gavras H., McKinstry D. N. A specific orally active inhibitor of angiotensin-converting enzyme in man. Lancet. 1977 Apr 9;1(8015):775–778. doi: 10.1016/s0140-6736(77)92958-0. [DOI] [PubMed] [Google Scholar]
  6. Gavras H., Brunner H. R., Turini G. A., Kershaw G. R., Tifft C. P., Cuttelod S., Gavras I., Vukovich R. A., McKinstry D. N. Antihypertensive effect of the oral angiotensin converting-enzyme inhibitor SQ 14225 in man. N Engl J Med. 1978 May 4;298(18):991–995. doi: 10.1056/NEJM197805042981803. [DOI] [PubMed] [Google Scholar]
  7. Ng K. K., Vane J. R. Conversion of angiotensin I to angiotensin II. Nature. 1967 Nov 25;216(5117):762–766. doi: 10.1038/216762a0. [DOI] [PubMed] [Google Scholar]
  8. Roulston J. E., MacGregor G. A. The measurement of angiotensin-converting enzyme in subjects receiving captopril. N Engl J Med. 1980 Aug 14;303(7):397–397. doi: 10.1056/NEJM198008143030717. [DOI] [PubMed] [Google Scholar]
  9. Turini G. A., Brunner H. R., Gribic M., Waeber B., Gavras H. Improvement of chronic congestive heart-failure by oral captopril. Lancet. 1979 Jun 9;1(8128):1213–1215. doi: 10.1016/s0140-6736(79)91897-x. [DOI] [PubMed] [Google Scholar]
  10. Waeber B., Brunner H. R., Brunner D. B., Curtet A. L., Turini G. A., Gavras H. Discrepancy between antihypertensive effect and angiotensin converting enzyme inhibition by captopril. Hypertension. 1980 Mar-Apr;2(2):236–242. doi: 10.1161/01.hyp.2.2.236. [DOI] [PubMed] [Google Scholar]
  11. Waite M. A. Measurement of concentrations of angiotensin I in human blood by radioimmunoassay. Clin Sci. 1973 Jul;45(1):51–64. doi: 10.1042/cs0450051. [DOI] [PubMed] [Google Scholar]

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