VASCULAR AND MYOCARDIAL PROTECTIVE EFFECTS OF CONVERTING-ENZYME INHIBITION IN EXPERIMENTAL HEART-FAILURE

Systemic vasoconstriction due to stimulation of the sympathetic and re nin-angiotensin-aldosterone systems is a hallmark of heart failure and this is accompanied by impaired endothelium-dependent relaxations at the level of large arteries. This study investigated, in a rat model o f heart failure, whether such an endothelial dysfunction also exists a t the level of the resistance artery, and whether this is associated w ith morphologic changes, as well as the effects of chronic treatment w ith the angiotensin-converting enzyme inhibitor perindopril (2 mg/kg/ day). After 12 months, arterial pressure, left ventricular (LV) end di astolic pressure (LVEDP), and LV dP/dt were measured in anesthetized r ats. Responses to acetylcholine and nitroprusside were determined in i solated and perfused mesenteric artery segments (diameter: 280 +/- 15 mu m). After fixation, vessel diameter, media cross-sectional area, an d media collagen and elastin densities were measured by image analysis . After 12 months, untreated rats showed signs of heart failure, i.e., reduced LV dP/dt, and increased LVEDP, heart weight/body weight, LV c avity circumference, and myocardial collagen density. In mesenteric ve ssels the endothelium-dependent vasodilator response to acetylcholine was impaired, whereas the response to the nitric oxide donor nitroprus side was unaffected. Heart failure did not affect vascular morphologic al parameters. Perindopril decreased blood pressure and LVEDP without any modification of LV dP/dt, and prevented cardiac remodeling. At the vascular level, perindopril improved the response to acetylcholine an d reduced media cross-sectional area and collagen density without affe cting internal vessel diameter or elastin density. Thus, heart failure decreases endothelium-dependent vasodilator response to acetylcholine without modification of vessel structure. The heart-failure induced e ndothelial dysfunction could be prevented by angiotensin-converting en zyme inhibition.