Angiotensin ii formation in dog heart is mediated by different
pathways in-vivo and in-vitro.
Balcells, Eduardo, Qing C. Meng, Gilbert Hageman, Ronald W. Palmer,
Joan N. Durand, Louis J. Dell'italia.
Birmingham Veteran Affairs Medical Center, University of Alabama at
Birmingham, Department of Medicine, Division of Cardiology,
University Station, Birmingham, Alabama 35294 and Department of
Physiology and Biophysics, University of Alabama at Birmingham
APStracts 3:0016H, 1996.
Angiotensin converting enzyme (ACE) inhibitors (I) have beneficial
effects that are presumably mediated by decreased angiotensin II (ANG
II) production. However, in-vitro assays in human heart extracts have
demonstrated that > 75% of ANG II forming enzyme activity was
not inhibited by captopril (cap), and therefore did not appear to be
related to ACE, but was inhibited by chymostatin, suggesting that it
was predominant chymase-like activity. Previous work in our
laboratory has demonstrated a similar relative contribution of ACE
and chymase-like activity toward ANG II formation in-vitro in dog
heart tissue extracts. Accordingly, we compared cap inhibitable ANG
II formation in-vitro in heart tissue of 5 adult mongrel dogs to the
in-vivo cap inhibitable ANG II forming activity across the myocardial
bed in 4 open-chested, adult mongrel dogs. In-vitro studies
demonstrated that only 6+2% of ANG II formation was inhibited by cap
from heart tissue extracts of the LV midwall. In in-vivo studies ANG
I (0.5 nmol/min) followed by ANG I + the ACEI cap (0.1 [mu]mol/min)
was infused into the left anterior descending artery and ANG II was
assayed in the proximal aorta and coronary sinus. The arterial-venous
difference (A-V diff) of ANG II across the myocardial circulation
increased significantly during ANG I infusion (-13.4+23.5 to
142.8+71.4 pg/ml, p<0.03). Subsequent coinfusion of cap with ANG
I significantly decreased the myocardial A-V diff of ANG II by 60+18%
(p<0.05). Thus, in contrast to the in-vitro situation, ANG II
formation in-vivo is inhibited significantly by cap in the normal dog
heart. This comparison of in-vivo and in-vitro conversion of ANG I to
ANG II by ACE and chymase-like activity suggests that in-vitro assays
may underestimate the functional contribution of ACE to intracardiac
ANG II formation.
Received 1 November 1995; accepted in final form 20 December
1995.
APS Manuscript Number H1026-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96