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CARDIOVASCULAR

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

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (N.R.T., S.W.W.); and Department of Pediatrics and Communicable Disease, University of Michigan, Ann Arbor, Michigan (C.E.G.)

Endothelin receptors (ET_A and ET_B) mediate responses to ET-1. ET_B receptor function seems to differ between a similarly sized arterial and venous pair, the rat vena cava (RVC) and rat thoracic aorta (RA). ET_B receptors mediate RVC contraction directly, but it is unclear whether ET_B receptors mediate contraction in RA. Because of these apparent differences in ET_B receptor-mediated vascular contraction, we hypothesize that relaxant ET_B-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-2 (PGF-2) (20 µM), the ET_B receptor agonist sarafotoxin-6c (S6c) (100 nM) significantly relaxed RA and RVC. N-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-2-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 ET_A receptor blockade. Vessels from dopamine-β-hydroxylase-ET_B transgenic rats, which lack functional ET_B receptors in the vasculature, were also used. RVC (PGF-2-contracted) from these rats did not relax to ET-1. Thus, although both RA and RVC possess endothelial relaxant ET_B receptors, RA and RVC differ in that relaxant ET_B receptors may also be present in smooth muscle of RVC. Moreover, the mechanisms of endothelial cell ET_B receptor-mediated relaxation in RA and RVC are not the same.

Address correspondence to: Nathan R. Tykocki, Department of Pharmacology and Toxicology, Michigan State University, B445 Life Sciences Bldg., East Lansing, MI 48824. E-mail: tykockin{at}msu.edu