Endothelial control of vascular tone in chronic heart failure

Patients with chronic heart failure (CHF) are hemodynamically characterized by increased vasoconstriction and a reduced vasodilator response to exerci se. In addition to various compensatory neurohumoral mechanisms, there is e vidence that the endothelium plays an important role in the abnormal vasodi lator response. This evidence comes from studies investigating the microvas cular response to regional, intraarterial administration of the endothelium -dependent vasodilator acetylcholine, which found that the vasodilator resp onse and therefore the bioavailability of nitric oxide (NO) was impaired in the microcirculation of the leg, forearm, and myocardium of patients with CHF. The mechanisms underlying this abnormal response are not entirely clea r but may reflect a muscarinic receptor abnormality. Because conduit artery vasodilatation during hyperemic blood flow is also impaired and because th is response is not dependent on muscarinic receptor activation, this possib ility appears to be unlikely. However, impaired smooth muscle responsivenes s to NO stimulation, impaired L-arginine availability or utilization, endot helial release of vasoconstricting prostanoids, increased NO degradation an d reduced NO synthase activity have all been implicated in this impaired re sponse. In addition, the vasoconstrictor activity of endothelin (ET)-1 appe ars to play an important role in the regulation of tone in CHF, although th e importance of different ET receptors is not yet clear.