5-Hydroxytryptamine-induced vasodilator responses in the hindquarters of the anaesthetized rat, involve beta2-adrenoceptors.
These studies were conducted to examine the role of the vasoactive mediators nitric oxide (NO) and adrenaline (epinephrine) in the serotonin (5-hydroxytryptamine; 5-HT)-induced vasodilator response in the hindquarter vascular bed of anaesthetized rats. Intra-arterial administration of doses of 5-HT in the range 0.12-25 ng kg(-1) produced a dose-independent vasodilator effect in the hindquarters. The selective 5-HT(1D/1B) receptor agonist, L-694,247 at intra-arterial doses of 0.0012-1000 ng kg(-1), as well as adrenaline (at doses of 0.05-50 ng kg(-1) i.a.), mimicked the dose-independent vasodilator effect induced by intra-arterial administration of 5-HT. Intravenous pre-treatment with the selective beta2-receptor antagonist ICI 118,551 (0.5 mg kg(-1)) blocked the vasodilator effect of 5-HT, adrenaline and L-694,247. Additionally, the inhibitor of NO synthase NG-nitro-L-arginine (L-NAME) (at a dose of 10 mg kg(-1) i.v.) blocked the vasodilator action of acetylcholine 300-3000 ng kg(-1)) but did not modify 5-HT-induced vasodilatation. The vasodilator effect produced by intra-arterial administration of 5-HT in the hindquarters was significantly inhibited both 30 min after denervation of the lumbar sympathetic chains and 1 h after bilateral adrenalectomy. Our data suggest that in the in-situ autoperfused hindquarters of the rat 5-HT-induced vasodilatation is mediated by a local 5-HT(1D) or 5-HT(1D/1B) activation, which in turn mediates the adrenal release of adrenaline, which then produces beta2-activation and vasodilatation.
Calama
E
E
Laboratorio de Farmacognosia y Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain.
García
M
M
Jarque
M J
MJ
Morán
A
A
Martín
M L
ML
San Román
L
L
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D016166:Free Radical Scavengers; D012702:Serotonin Antagonists; D009569:Nitric Oxide; D012701:Serotonin; D004837:Epinephrine