5‐ HT modulates the rat mesenteric vasopressor outflow by 5‐HT1Dsympatholytic receptors

Summary 5‐hydroxytryptamine (5‐HT) modulates noradrenergic activity in different cardiovascular territories, but its effect on the mesenteric vasopressor outflow has not yet been clarified. This study investigated the in vivo serotonergic influence, characterizing 5‐HTreceptors implicated, in sympathetic innervation of mesenteric vasculature. Wistar rats were anaesthetised and prepared for the in situ autoperfused rat mesentery, monitoring systemic blood pressure (SBP), heart rate (HR) and mesenteric perfusion pressure (MPP). Electrical stimulation of mesenteric sympathetic nerves resulted in frequency‐dependent increases inMPP(9 ± 1.6, 25.7 ± 3.9 and 60.2 ± 5 mmHg for 2, 4 and 8 Hz, respectively), without alteringSBPorHR. 5‐HT(1‐25 μg/kg), 5‐carboxamidotryptamine (5‐HT1/7agonist; 25 μg/kg) or L‐694,247 (5‐HT1Dagonist; 1‐25 μg/kg) i.a. bolus inhibited vasopressor responses by mesenteric nerves electrical stimulation, unlike i.a. bolus of agonists 8‐OH‐DPAT(5‐HT1A), CGS‐12066B (5‐HT1B), BRL 54443 (5‐HT1e/1F), α‐methyl‐5‐HT(5‐HT2), 1‐PBG(5‐HT3), cisapride (5‐HT4) orAS‐19 (5‐HT7) (25 μg/kg each). Interestingly, i.a. L‐694,247 (25 μg/kg) also reduced the exogenous norepinephrine‐induced vasoconstrictions. Pretreatment with selective 5‐HT1Dreceptor antagonist,LY310762 (1 mg/kg, i.v.), completely abolished L‐694,247‐ and 5‐HT‐induced mesenteric sympathoinhibition. Furthermore,ELISAanalysis confirmed 5‐HT1Dreceptors expression in mesenteric artery. These findings suggest that serotonergic mechanisms‐induced sympathoinhibition of mesenteric noradrenergic outflow is mediated by pre and/or postjunctional 5‐HT1Dreceptors.