Is renin a factor in the etiology of essential hypertension?

Journal Article

The widespread clinical study of converting-enzyme inhibitors has shown that they are effective antihypertensive drugs even in patients who may manifest either normal or decreased plasma renin activity. This suggests either that renin in a site other than plasma may play a contributory role in essential hypertension or that the hypotensive effect is caused by increased concentrations of kinins and prostaglandins, both demonstrated consequences of converting-enzyme inhibitor administration. Specific renin inhibitors appropriate for studies in humans would aid in the resolution of this question. Four classes of compounds have been demonstrated to be renin inhibitors of high potency: specific antibody, general peptide inhibitors of acid proteases, analogy of angiotensinogens, and peptides that are related to the amino-terminal sequence of prorenin. With the purification of renin, specific polyclonal or monoclonal antibodies have become available. The former have already been used extensively in physiologic studies in intact animals. Pepstatin is an inhibitor of many acid proteases. Its in vivo application has been retarded by its relative insolubility, but recent chemical modifications, particularly the addition of charged amino acids at the carboxy terminus, have rendered it more useful. The minimal substrate for renin is an octapeptide segment of the protein substrate: His-Pro-Phe-His-Leu-Leu-Val-Tyr. Variants of this sequence have resulted in competitive inhibitors that are useful in vivo. Recently, remarkably active inhibitors have been synthesized by reducing the peptide bond that is cleaved by renin, producing what may be a transition state inhibitor. Several of these peptides have been shown to be effective as in vivo inhibitors of the hypertensive effect of the enzyme. The development of inhibitors based on prorenin sequences is awaited with interest. Substrate analog inhibitors have now been studied in dogs and monkeys, and, most recently, preliminary studies have human been reported in humans. A hypotensive response has been demonstrated in sodium-replete, normal human subjects as well as in a low-renin hypertensive subject. The mechanism of this unexpected finding needs to be explained.

Duke Authors

Cited Authors

  • Haber, E; Zusman, R; Burton, J; Dzau, VJ; Barger, AC

Published Date

  • 1983

Published In

Volume / Issue

  • 5 / 6 III

Start / End Page

  • V-8-V-15 -

International Standard Serial Number (ISSN)

  • 0194-911X