PREVENTION OF ENDOTHELIAL DYSFUNCTION IN SMALL AND LARGE ARTERIES IN A MODEL OF CHRONIC HEART-FAILURE - EFFECT OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION

Chronic heart failure (CHF) impairs endothelium-dependent vasodilatati on of large conductance arteries. We investigated whether a similar re duction also occurs in small arteries, and whether such a reduction ca n be prevented by the angiotensin converting enzyme inhibitor perindop ril (P) in a rat model of CHF (left coronary artery ligation). After 1 month treatment with placebo or P (2 mg/kg/day), rats were anesthetiz ed and arterial pressure, left ventricular end-diastolic pressure, and central venous pressure were measured with a micromanometer. Segments of aorta and mesenteric artery (mean diameter, 281 +/- 8 mu m) were t hen isolated, cannulated, and perfused at constant pressure using an a rteriograph. Responses to increasing concentrations of acetylcholine ( Ach), nitroprusside, and to 10(-4) mol/L N-G-nitro-L-arginine methyl e ster (L-NAME) were studied after preconstriction by phenylephrine. Hea rt failure resulted in a decrease in systolic and diastolic pressures, an increase in left ventricular end-diastolic and central venous pres sures, and a significant depression of Ach-induced dilatation of the m esenteric artery (maximal dilatation, from 90 +/- 4% to 63 +/- 4%, P<. 05) but not of the aorta (from 56 +/- 870 to 45 +/- 570, NS) without a ny modification in the endothelium-independent vasodilatation induced by nitroprusside. In the group treated by the angiotensin converting e nzyme (ACE) inhibitor perindopril, systolic and diastolic pressures we re slightly decreased, whereas left ventricular end diastolic, central venous pressures, and the endothelium-dependent vasodilating response to Ach were normalized. Responses to L-NAME were not affected by CHF or perindopril. Perindopril also decreased hypertrophy, as evidenced b y a significantly lower heart weight in treated rats. Thus, CHF decrea ses the endothelium-dependent response to Ach, which is heterogeneous and mainly affects small arteries, whereas the basal release of NO app ears unaffected. This CHF-induced dysfunction could be prevented by ch ronic ACE inhibition.