Inhibition of Human Plasma Renin Activity by Pepstatin

Abstract

Pepstatin, a pentapeptide isolated from streptomyces, is a powerful inhibitor of several acid proteases. Its ability to inhibit the reninangiotensinogen reaction was studied in vitro, in various human plasma. A 50% inhibition of plasma renin activity was obtained with 10-⁶M pepstatin at pH 5.7 and 10 ⁵M at pH 7.4. The inhibition of plasma renin activity by pepstatin was studied in hypertensive patients with various plasma renin levels. The inhibitory effect could be demonstrated in patients with low, normal and high renin activity at both pH's. The type of inhibition and the inhibitory constant were investigated by Dixon plot and Lineweaver-Burk plot in three separate experiments. On both representations, a competitive type of inhibition was found with an inhibitory constant of about 1.2 × 10-⁶M.