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(Hypertension. 1997;30:830-836.)
© 1997 American Heart Association, Inc.

Articles

Reversal of Endothelin-1 Release by Stimulation of Endothelial ₂-Adrenoceptor Contributes to Cerebral Vasorelaxation

Eric Thorin; S. Martin Shreeve; Nathalie Thorin-Trescases; ; John A. Bevan

From The Totman Laboratory for Human Cerebrovascular Research, Department of Pharmacology, Given Building, University of Vermont (Burlington).

Abstract Agonists acting on the vascular endothelium can modulate the release of a number of factors that interact with the surrounding smooth muscle cells and influence their tone. One such factor is the vasoconstricting agent endothelin-1 (ET-1), which has been implicated in several disease states, including stroke. However, very little is known about the physiological role of ET-1 in the cerebral circulation. We demonstrate that activation of ₂-adrenoceptors in human pial artery endothelial cells reduces both constitutive and agonist-stimulated release of immunoreactive ET-1. That this has physiological relevance is supported by our demonstration that in segments of rabbit middle cerebral arteries, ₂-adrenoceptor activation reduces the release of endothelium-derived ET-1 and causes an endothelium-dependent relaxation. The adrenoceptor-dependent relaxation was not blocked by combined addition of indomethacin and N-nitro-L-arginine in 25 mmol/L KCl-depolarizing physiological solution but was selectively antagonized by a subthreshold concentration of exogenous ET-1. Our data suggest that activation of endothelial ₂-adrenoceptor would favor a decrease in ET-1 production and possibly promote vascular relaxation.

Key Words: endothelium • artery, cerebral • receptors, adrenergic • endothelin-1 • human • rabbits

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