APStracts 3:0503H, 1996.

Pressure independent effects of at1 receptor antagonism on cardiovascular remodeling in aortic-banded rats. Regan, Christopher P., Peter G. Anderson, Sanford P. Bishop, Kathleen H. Berecek. Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294

APStracts 3:0503H, 1996.

To determine the role of angiotensin II receptor blockade on cardiovascular remodeling in a pressure overload model of cardiac hypertrophy, a subdiaphragmatic aortic band was placed in adult, male, Sprague Dawley rats. Aortic-banded rats were left untreated (AB), or given losartan (Los, 250mg/L) (AB-Los). Sham-operated controls were either left untreated (S) or given Los (S-Los). After 4 weeks, rats were catheterized for measurement of carotid and femoral mean arterial pressures (CMAP and FMAP in mmHg, respectively). Hearts were perfused on a modified Langendorff system and minimal coronary resistance (MCR) determined. Hearts were then perfusion-fixed, total and regional heart weights recorded, and sections were processed for morphology. Changes in coronary artery medial thickness and perivascular fibrosis were assessed by quantitative image analysis. CMAP was significantly higher in AB and AB-Los than S or S-Los (p&LT;0.05). There was no difference in FMAP in AB vs. S, but AB -Los and S-Los had lower FMAP's than S. Total heart weight and left ventricular weight / body weight ratios were increased in AB and AB -Los compared to S and S-Los (p&LT;0.05). MCR of AB was greater than S and S-Los. MCR of AB-Los was significantly lower than AB and was not significantly different from S and S-Los. In coronary vessels, medial thickness was greatest in AB, while there was no difference among AB-Los, S, and S-Los. Similarly, the increase in perivascular fibrosis was greatest in AB and there was no difference among AB-Los, S, and S-Los. These data suggest that angiotensin II, independent of increased arterial pressure, is critical for the development of the vascular and fibrotic changes that occur in this model of pressure overload hypertrophy.

Received 23 August 1996; accepted in final form 20 November 1996.
APS Manuscript Number H804-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996