5-Hydroxytryptamine-induced vasodilator responses in the hindquarters of the anaesthetized rat, involve β2-adrenoceptors

Abstract

Abstract 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-HT1D/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 β2-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-HT1D or 5-HT1D/1B activation, which in turn mediates the adrenal release of adrenaline, which then produces β2-activation and vasodilatation.