Endothelin-A receptor antagonist-mediated vasodilatation is attenuated by inhibition of nitric oxide synthesis and by endothelin-B receptor blockade

Article

关键词: CHRONIC HEART-FAILURE;    SMOOTH-MUSCLE CELLS;    HUMAN BLOOD-VESSELS;    CAPACITANCE VESSELS;    BIG ENDOTHELIN-1;    RELAXING FACTOR;    ET(B) RECEPTOR;    IN-VIVO;    VASOCONSTRICTION;    FOREARM;   

DOI  :  10.1161/01.CIR.97.8.752

来源: SCIE

【 摘 要 】

Background-The role of endothelin (ET)-1 ill maintenance of basal vascular tone has been demonstrated by local and systemic vasodilatation to endothelin receptor antagonists in humans. Although the constrictor effects mediated bg the vascular smooth muscle ETA receptors are clear, the contribution from endothelial and vascular smooth muscle ETB receptors remains to be defined. The present study, in human forearm resistance vessels in vivo, was designed to further investigate the physiological function of ETA and ETB receptor subtypes ill human blood vessels and determine the mechanism underlying the vasodilatation to the ETA-selective receptor antagonist BQ-123. Methods and Results-Two studies were performed, each in groups of eight healthy subjects. Brachial artery infusion of BQ-123 caused significant forearm vasodilatation in both studies, This vasodilatation was reduced by 95% (P=.006) with inhibition of the endogenous generation of nitric oxide and by 38% (P<.001) with coinfusion of the ETB receptor antagonist BQ-788. In contrast, inhibition of prostanoid generation did not affect the response to BQ-123. Infusion of BQ-788 alone produced a 20% reduction in forearm blood now (P<.001). Conclusions-Selective ETA receptor antagonism causes vasodilatation of human forearm resistance vessels in vivo, This response appears to result in major part front an increase ill nitric oxide generation. ETB receptor antagonism either alone or on a background of ETA antagonism causes local vasoconstriction, indicating that ETB receptors in blood vessels respond to ET-1 predominantly causing vasodilatation.

【 授权许可】

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