ENDOTHELIAL FUNCTION IN CONGESTIVE-HEART-FAILURE

There is evidence that the endothelium plays an important role in the control of human vascular tone by releasing endothelium-derived nitric oxide and, therefore, a defective endothelial function could be invol ved in the increased peripheral vasoconstriction of patients with chro nic congestive heart failure. To investigate endothelial function in h umans in vivo, agents such as acetylcholine, a short-acting stimulator of the release of endothelium-derived nitric oxide, has been used. Co nversely, N-mono-methyl-L-arginine, a specific inhibitor of nitric oxi de synthesis froM L-arginine, has recently been shown to decrease bloo d flow during infusion into the brachial artery of healthy volunteers (control subjects) by inhibiting the basal release of nitric oxide. Co nsistent with experimental studies, the blood flow response to acetylc holine is blunted in patients with chronic heart failure compared with healthy age-matched volunteers. In contrast, the decrease in blood fl ow induced by N-mono-methyl-L-arginine appears to be exaggerated in co ngestive heart failure. The blood flow response to nitroglycerin or so dium nitroprusside, endothelium-independent vasodilators, is usually p reserved in patients with chronic, nonedematous heart failure, indicat ing a normal response of the vascular smooth muscle of resistance vess els to exogenous nitric oxide. In contrast, the dilator response of th e radial artery diameter to nitroglycerin and flow-dependent dilation is impaired in patients with chronic heart failure, indicating that th e abnormal flow-mediated relaxation of large arteries may be caused by both endothelial and structural abnormalities. Thus impaired endothel ium-dependent dilation of peripheral resistance vessels emerges in chr onic heart failure, suggesting a reduced release of nitric oxide on st imulation; the latter (defective) mechanism may be involved in the imp aired vasodilator capacity in the peripheral circulation (e.g., during exercise). In contrast, the basal release of nitric oxide from endoth elium of resistance vessels appears to be preserved or may even be enh anced and may play an important compensatory role in chronic heart fai lure during resting conditions by antagonizing neurohumoral vasoconstr ictor forces.