Endothelin ET(B) receptors in arteries and veins: multiple actions in the vein.
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-2alpha (PGF-2alpha) (20 microM), the ET(B) receptor agonist sarafotoxin-6c (S6c) (100 nM) significantly relaxed RA and RVC. N(omega)-Nitro-L-arginine (LNNA) (100 microM) 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-2alpha-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-beta-hydroxylase-ET(B) transgenic rats, which lack functional ET(B) receptors in the vasculature, were also used. RVC (PGF-2alpha-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.
Tykocki
Nathan R
NR
Department of Pharmacology and Toxicology, Michigan State University, B445 Life Sciences Bldg., East Lansing, MI 48824, USA. tykockin@msu.edu
Gariepy
Cheryl E
CE
Watts
Stephanie W
SW
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D000077868:Atrasentan; D015237:Dinoprost / Q000494:pharmacology; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D019335:Nitroarginine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000819:agonists / Q000502:physiology*; D017539:Tunica Intima / Q000378:metabolism; D017540:Tunica Media / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014684:Venae Cavae / Q000187:drug effects / Q000502:physiology*; D014757:Viper Venoms / Q000494:pharmacology
D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010880:Piperidines; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; D019335:Nitroarginine; C086539:BQ 788; D015237:Dinoprost; D000077868:Atrasentan