RESPONSE OF LARGE AND SMALL VESSELS TO ALPHA-ADRENOCEPTOR AND BETA-ADRENOCEPTOR STIMULATION IN HEART-FAILURE - EFFECT OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION

The increased sympathetic drive in chronic heart failure (CHF) might p rovoke vascular adrenoceptor desensitization, which, together with end othelial dysfunction, could contribute to the altered vasomotor tone s een in CHF. We investigated 1) whether CHF alters the responses mediat ed by alpha and beta adrenoceptors in small and large peripheral arter ies, and 2) the effect of angiotensin-converting enzyme (ACE) inhibiti on. Rats with CHF (coronary artery ligation) were treated with placebo or the ACE inhibitor lisinopril (10 mg/kg/d) starting 7 days after li gation. Responses to phenylephrine (alpha(1) agonist), salbutamol (bet a(2) agonist) as well as acetylcholine (endothelium-dependent), were a ssessed after 3 months in isolated and pressurized segments of the abd ominal aorta, the femoral and the mesenteric arteries. In animals with hemodynamic signs of CHF, neither the vasoconstrictor responses to ph enylephrine nor the vasodilator response to salbutamol were affected. In contrast, the dilator response to acetylcholine of both small arter ies, but not that of the aorta, was impaired. Furthermore, CHF did not modify vessel structure. While lisinopril did not modify the response s to adrenergic agonists, it normalized the response to acetylcholine. Furthermore, ACE inhibition reduced vascular media cross sectional ar ea and collagen density. Thus, the unchanged arterial responsiveness t o adrenoceptor agonists does not indicate any vascular adrenoceptor de sensitization, while endothelial dependent vasodilation of small arter ies is impaired in CHF. ACE inhibition does not modify the response to adrenergic stimuli, prevents endothelial dysfunction and induces both cardiac and vascular remodeling, which probably contribute to the eff ect ACE inhibitors have on exercise tolerance and survival.