PRESSURE-INDEPENDENT EFFECTS OF AT(1)-RECEPTOR ANTAGONISM ON CARDIOVASCULAR REMODELING IN AORTIC-BANDED RATS

To determine the role of angiotensin II-receptor blockade on cardiovas cular remodeling in a pressure-overload model of cardiac hypertrophy, a subdiaphragmatic aortic band was placed in adult male Sprague-Dawley rats. Aortic-banded (AB) rats were left untreated or were losartan (L os; 250 mg/l) treated (AB-Los). Sham-operated (S) controls were either left untreated or treated with Los (S-Los). After 4 wk, rats were cat heterized for measurement of mean arterial pressures [carotid (CMAP) a nd femoral (FMAP), in mmHg]. Hearts were perfused on a modified Langen dorff system, and minimal coronary resistance (MCR) was determined. He arts were then perfusion fixed, total and regional heart weights were recorded, and sections were processed for morphology. Changes in coron ary artery medial thickness and perivascular fibrosis were assessed by quantitative image analysis. CMAP was significantly higher in AB and AB-Los than in S or S-Los (P < 0.05). There was no difference in FMAP in AB vs. S, but AB-Los and S-Los had lower FMAPs than S. Total heart weight and left ventricular weight-to-body weight ratios were increase d in AB and AB-Los compared with S and S-Los (P < 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 v essels, medial thickness was greatest in AB, whereas there was no diff erence among AB-Los, S, and S-Los. Similarly, the increase in perivasc ular fibrosis was greatest in AB, and there was no difference among AB -Los, S, and S-Los. These data suggest that angiotensin II, independen t of increased arterial pressure, is critical for the development of t he vascular and fibrotic changes that occur in this model of pressure- overload hypertrophy.