Inhibitory Effects of Kinins on Angiotensin I Conversion in the Local Circulation

Abstract

The inhibition of angiotensin converting enzyme (ACE) by kinins was studied using bradykinin (BK), lysyl-bradykinin (Lys-BK), [Hydroxyproline3]-bradykinin ([Hyp3]-BK) and [Hydroxyproline3]-lysyl-bradykinin ([Hyp3]-Lys-BK). The latter two are novel kinins recently identified in our laboratory. All the four kinins displayed competitive inhibition on the conversion of angiotensin I to angiotensin II by purified canine lung ACE. Inhibition constants (Ki) for the four kinins were estimated from Dixon's plot as follows-BK: 0.27 microM, Lys-BK: 0.57 microM, [Hyp3]-BK: 0.34 microM, and [Hyp3]-Lys-BK: 0.27 microM. In the rat hindlimb perfusion system, the kinins were demonstrated to partially inhibit angiotensin I conversion to angiotensin II by the vascular ACE. Taken together, these results suggest that angiotensin II formation by ACE in the vascular tissue is possibly inhibited by local kinins, especially after ACE inhibitor administration. This indirect action of kinins, coupled with its direct vasodilatory action, might indicate a cooperative participation in vasodilation.