Strong diuretic effect of pepstatin, an acid protease inhibitor.

Publisher Website
Google Scholar
Abstract
Pepstatin, an acid protease inhibitor purified from the culture medium of an actinomycete, had a strong diuretic effect in C3H/He mice. A single s.c. injection of pepstatin at 80 mg/kg body wt caused a 3- to 4-fold increase in the urine volume when compared to control mice during the first 24 h after injection and a 6- to 7-fold increase during the second and third 24 h periods. The effect was maximal after 72-96 h, and gradually disappeared within 168 h after injection. The serum K+ concentration increased to 7.6 meq/l at 24 h after injection but the serum Na+ concentration did not change significantly. Electrolyte changes disappeared within 168 h after injection. The soluble derivative of pepstatin, lactyl-pepstatin, which has a higher ID50 [mean inhibitory dose] than pepstatin for renin, had no significant diuretic effect at the same molar dose. Apparently, the strong diuretic effect of pepstatin is due to inhibition of renin-mediated conversion of angiotensinogen to angiotensin I, which in turn is normally converted to angiotensin II, resulting in release of aldosterone.

This publication has 0 references indexed in Scilit: