A SUBSTRATE-ANALOG INHIBITOR OF RENIN THAT IS EFFECTIVE INVIVO

Abstract

A potent inhibitor of primate renin effective in vivo has been synthesized. The peptide, Pro-His-Pro-Phe-His-Phe-Phe-Val-Tyr-Lys, is an analog of the amino acid sequence found between residues 6 and 13 of renin natural substrate (angiotensinogen). The inhibitor is eight times more soluble at physiologic pH and is cleared from circulation about two-orders of magnitude more slowly than earlier substrate analog inhibitors which were not active in vivo. Infusion of the inhibitor into the monkey (M. fascicularis) blocks the rise in mean arterial pressure caused by exogenous human renin, but not by angiotensin I or II. When injected into a salt-depleted monkey, the peptide lowers blood pressure in..