Influence of the thromboxane-mimetic U-46619 and the prostacyclin metabolite 6-keto prostaglandin E1 on vasoconstriction induced by noradrenaline and 5-HT in rat mesenteric vasculature.
The aim of this study was to investigate the effects of U-46619, a thromboxane A2-mimetic, and 6-keto prostaglandin E1 (6-keto PGE1) a biologically active metabolite of prostacyclin, on vasoconstrictor responses to noradrenaline and 5-hydroxytryptamine (5-HT). In vitro, U-46619 (3-100 nmol/l) amplified responses to both noradrenaline and 5-HT in a concentration-dependent manner. This effect was not caused by an increase in the affinity of the alpha-adrenoceptor for noradrenaline because U-46619 (100 nmol/l) did not alter the pA2 of phentolamine. In vivo, U-46619 (100 nmol/l) induced vasoconstriction and consequently significantly shifted the log-concentration-effect curves to noradrenaline and 5-HT upward in an additive manner. 6-Keto PGE1 (1 mumol/l) did not affect either perfusion pressure or vasoconstriction in response to noradrenaline in vivo. The study highlights some differences in responses between in vitro- and in vivo-perfused mesentery.
Stanton
B J
BJ
School of Pharmacology, Victorian College of Pharmacy, Parkville, Australia.
Coupar
I M
IM
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D011450:Prostaglandin Endoperoxides, Synthetic; D012701:Serotonin; D013928:Thromboxane A2; C022950:6-ketoprostaglandin E1; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000527:Alprostadil; D009638:Norepinephrine