Vasoconstriction by in situ formed angiotensin II: role of ACE and chymase

Objective: To assess the importance, for vasoconstriction, of in situ angio tensin (Ang) II generation, as opposed to Ang LI delivery to AT receptors v ia the organ bath fluid, Methods: Ang I and II concentration-response curve s in human and porcine coronary arteries (HCAs, PCAs) were constructed in r elation to estimates of the clearances of Ang I and II (Cl-AngI Cl-AngII) f rom the organ bath and the release of newly formed Ang II (R-AngII) into th e bath fluid. HCAs were from 25 heart valve donors (age 5-54 years), and PC As from 14 pigs (age 3 months). Results: Ang I- and II-evoked constrictions were inhibited by the AT(1) receptor antagonist, irbesartan, and were not influenced by the AT(2) receptor antagonist, PD123319. In HCAs Ang II was o nly three times more potent than Ang I, whereas, in the experiments with An g I, comparison of Cl-AngI with Cl-AngII and R-AngII indicated that most of the arterially produced Ang II did not reach the bath fluid. Also in PCAs Ang I and II showed similar potency. In HCAs both the ACE inhibitor, captop ril, and the chymase inhibitor, chymostatin, inhibited Ang I-evoked vasocon striction, while only chymostatin had a significant effect on Cl-AngI. In P CAs Ang I-evoked vasoconstriction was almost completely ACE-dependent. Conc lusions: This study points towards the functional importance of in situ ACE - and chymase-dependent Ang LI generation, as opposed to Ang II delivery vi a the circulation. It also indicates that functionally relevant changes in local Ang I-II conversion are not necessarily reflected by detectable chang es in circulating Ang II. (C) 1999 Elsevier Science BN. All rights reserved .