ETB receptor activation changes ETB receptor location in venous but not aortic smooth muscle cells

Abstract

Endothelin (ET‐1) is a 21‐amino acid peptide that acts as a potent endogenous vasoconstrictor, and is produced by vascular endothelial cells. ET‐1 activates two G‐protein coupled receptor subtypes: ETA and ETB. In arteries, ETA receptor stimulation causes contraction and ETB stimulation causes relaxation. Although ETA stimulation also causes contraction in veins, ETB stimulation can cause either contraction or relaxation. Since ETB receptors cause contraction in veins but not arteries, we hypothesize that venous smooth muscle ETB receptors will relocate within cells in ways arterial ETB receptors do not.Explants of aortic and venous smooth muscle cells (SMC) were cultured from freshly dissected rat thoracic aorta and vena cava. Cells were exposed to vehicle or the ETB receptor agonist Sarafotoxin‐6c (S6c) (100 nM) for 30 minutes prior to immunofluorescent labeling of ETA receptors, ETB receptors, and nuclei. Untreated aortic and venous SMC expressed ETA and ETB receptors, without significant difference in receptor mean fluorescence. In the presence of S6c, mean ETB receptor fluorescence was significantly greater in nuclei of venous SMC when compared to aortic SMC (137.6±9.4 vs. 96.3±11.5). S6c did not alter ETA or ETB whole‐cell fluorescence in aortic and venous SMC. These findings imply a role of activated ETB receptors in S6c‐induced signaling in venous smooth muscle cells.