Role of endothelins in regulation of vascular tone in the in situ perfused rat adrenals

Abstract

This study examined the role of endothelins (ETs) and their receptor subtypes ETAand ETB in the regulation of vascular tone in the in situ perfused rat left adrenal gland. Endothelin-1 (ET-1), which binds both ETA and ETB receptors, decreased adrenal flow rate of the perfusion medium, and its effect was reversed by the ETA antagonist BQ-123 and enhanced by the ETB antagonist BQ-788. ET-3, which preferentially binds ETB, and the selective ETB agonist BQ-3020 increased adrenal flow rate of perfusate, and their effects were annulled by BQ-788. BQ-123 magnified the effect of ET-3 and did not affect that of BQ-3020. The ETA-mediated decrease and the ETB-mediated rise in the rate of collection of perfusate were abolished by Ro-31–8220, an inhibitor of protein kinase C (PKC), and by N G-nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase (NOS), respectively. Collectively, these findings suggest that ETs can regulate vascular tone in the in situ perfused rat adrenals via both PKC-coupled ETA and NOS-coupled ETB receptors, the activation of which evokes vasoconstriction and vasodilation, respectively.