Affiliation:
1. From the University of Edinburgh (UK), Department of Medicine, Western General Hospital.
Abstract
Background
The role of endothelin ET
B
receptors in mediating vasoconstriction in humans is unclear. As yet, there have been no in vivo studies in resistance vessels, and in vitro data have been contradictory. We therefore investigated the function of ET
B
receptors in vivo in human forearm resistance and hand capacitance vessels using endothelin-1 as a nonselective agonist at ET
A
and ET
B
receptors and endothelin-3 and sarafotoxin S6c as selective agonists at the ET
B
receptor.
Methods and Results
A series of single-blind studies were performed, each in six healthy men. Brachial artery infusion of endothelin-1 and endothelin-3 caused slow-onset dose-dependent forearm vasoconstriction. Although endothelin-3 caused significantly less forearm vasoconstriction than endothelin-1 at low doses, vasoconstriction was similar to the two isopeptides at the highest dose (60 pmol/min). Endothelin-3 caused transient forearm vasodilatation at this dose, whereas endothelin-1 showed only a nonsignificant trend toward causing early vasodilatation. Intra-arterial sarafotoxin S6c caused a progressive reduction in forearm blood flow, although less than that to endothelin-1 (
P
=.04). Dorsal hand vein infusion of sarafotoxin S6c caused local venoconstriction that was also less than that to endothelin-1 (
P
=.002).
Conclusions
Selective ET
B
receptor agonists cause constriction of forearm resistance and hand capacitance vessels in vivo in humans, suggesting that both ET
A
and ET
B
receptors mediate vasoconstriction. Hence, antagonists at both ET
A
and ET
B
receptors, or inhibitors of the generation of endothelin-1, may be necessary to completely prevent vasoconstriction to endogenously generated endothelin-1.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
257 articles.
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