In vitro inhibition of renin by human des-angiotensin I renin substrate.

Human des-angiotensin I renin substrate, a cleavage product of the renin reaction, was generated in plasma and from semipurified renin substrate by exhaustive incubation with renin and was quantitated by a direct RIA. An increase in the Michaelis-Menten constant of the renin-substrate reaction, from 2000 to 5000 ng angiotensin I equivalents of renin substrate/ml, with no change in maximal velocity was observed upon addition of this semipurified protein to plasma. It is suggested that this phenomenon of competitive inhibition of the renin reaction by des-angiotensin I renin substrate accounts for discrepancies in the determination of renin substrate concentration and possibly has physiological significance for feedback inhibition of angiotensin I generation.