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 exercise. In addition to various compensatory neurohumoral mechanisms, there is evidence that the endothelium plays an important role in the abnormal vasodilator response. This evidence comes from studies investigating the microvascular response to regional, intra-arterial administration of the endothelium-dependent vasodilator acetylcholine, which found that the vasodilator response 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 clear but may reflect a muscarinic receptor abnormality. Because conduit artery vasodilatation during hyperemic blood flow is also impaired and because this response is not dependent on muscarinic receptor activation, this possibility appears to be unlikely. However, impaired smooth muscle responsiveness to NO stimulation, impaired L-arginine availability or utilization, endothelial release of vasoconstricting prostanoids, increased NO degradation and reduced NO synthase activity have all been implicated in this impaired response. In addition, the vasoconstrictor activity of endothelin (ET)-1 appears to play an important role in the regulation of tone in CHF, although the importance of different ET receptors is not yet clear.
Kiowski
W
W
Department of Medicine, University Hospital, University of Zurich, Switzerland.
Sütsch
G
G
Schalcher
C
C
Brunner
H P
HP
Oechslin
E
E
D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D009129:Muscle Tonus / Q000502:physiology; D014666:Vasomotor System / Q000503:physiopathology*