Endothelin ETB Receptors in Arteries and Veins: Multiple Actions in the Vein

AUTOR(ES)
FONTE

American Society for Pharmacology and Experimental Therapeutics

RESUMO

Endothelin receptors (ETA and ETB) mediate responses to ET-1. ETB receptor function seems to differ between a similarly sized arterial and venous pair, the rat vena cava (RVC) and rat thoracic aorta (RA). ETB receptors mediate RVC contraction directly, but it is unclear whether ETB receptors mediate contraction in RA. Because of these apparent differences in ETB receptor-mediated vascular contraction, we hypothesize that relaxant ETB-receptor mechanisms in RVC would be different from those in RA. RA and RVC rings were isolated from rats for measurement of isometric contraction. When contracted with prostaglandin F-2α (PGF-2α) (20 μM), the ETB receptor agonist sarafotoxin-6c (S6c) (100 nM) significantly relaxed RA and RVC. Nω-Nitro-l-arginine (LNNA) (100 μM) or endothelial denudation abolished relaxation to S6c in RA. By contrast, S6c-induced relaxation of RVC was attenuated but not abolished by LNNA and endothelial denudation. RVC (PGF-2α-contracted) relaxed to low concentrations of ET-1, whereas under the same conditions RA responded with contraction. ET-1-induced relaxation in RA was observed only with ETA receptor blockade. Vessels from dopamine-β-hydroxylase-ETB transgenic rats, which lack functional ETB receptors in the vasculature, were also used. RVC (PGF-2α-contracted) from these rats did not relax to ET-1. Thus, although both RA and RVC possess endothelial relaxant ETB receptors, RA and RVC differ in that relaxant ETB receptors may also be present in smooth muscle of RVC. Moreover, the mechanisms of endothelial cell ETB receptor-mediated relaxation in RA and RVC are not the same.

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