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(Circulation. 1995;92:357-363.)
© 1995 American Heart Association, Inc.

Articles

Endothelin ET_A and ET_B Receptors Cause Vasoconstriction of Human Resistance and Capacitance Vessels In Vivo

William G. Haynes, BSc, MD, MRCP; Fiona E. Strachan, BN, RGN; David J. Webb, MD, FRCP, FFPM

From the University of Edinburgh (UK), Department of Medicine, Western General Hospital.

Correspondence to Dr David J. Webb, University Department of Medicine, Western General Hospital, Edinburgh EH4 2XU, UK. E-mail d.j.webb@ed.ac.uk.

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.

Key Words: endothelin • vasoconstriction • vessels

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