EFFECT OF ACE-INHIBITION ON ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH CHRONIC HEART-FAILURE

The endothelium controls vascular smooth muscle tone by secreting rela xing and contracting factors. There is a constant release of endotheli um-derived relaxing: factor(s) (EDRF) under basal conditions. In addit ion, the endothelium can increase the release of EDRF in response to h umoral stimulation by vasoactive substances such as acetylcholine or b radykinin. Under physiological conditions the most important stimulus to the release of EDRF is an increase in blood flow, leading to increa sed shear stress on endothelial cells. Recent experimental studies hav e raised the possibility that bradykinin plays an important role in th e regulation of vascular tone at rest and during flow-stimulated condi tions. Bradykinin is a very potent vasodilator that exerts its vasodil atory actions by causing endothelial release of nitric oxide, prostacy clin and/or endothelium-derived hyperpolarizing factor. Recent studies in humans have demonstrated that bradykinin contributes to the regula tion of coronary vascular tone under resting and flow-stimulated condi tions. This mechanism has been shown to be important in humans in both peripheral and coronary arteries. Angiotensin-converting enzyme (ACE) inhibitors not only decrease angiotensin II but also increase bradyki nin levels, since ACE is identical to kininase II, which degrades brad ykinin. The beneficial vascular effects of ACE inhibitors may therefor e be related to increased availability of bradykinin. Indeed, we have recently shown that ACE inhibition improves flow-dependent, endotheliu m-mediated vasodilation and that this beneficial effect is bradykinin- dependent. Our preliminary data also indicate that ACE inhibition impr oves endothelium-mediated vasodilation in patients with heart failure and coronary artery disease due to an enhanced availability of nitric oxide. These findings suggest that the beneficial vascular effects of ACE inhibition in heart failure may be due in part to improved endothe lial function.