5-HT modulates the rat mesenteric vasopressor outflow by 5-HT1D sympatholytic receptors

Abstract

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-HT receptors 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 in MPP (9 ± 1.6, 25.7 ± 3.9 and 60.2 ± 5 mmHg for 2, 4 and 8 Hz, respectively), without altering SBP or HR. 5-HT (1-25 μg/kg), 5-carboxamidotryptamine (5-HT_1/7 agonist; 25 μg/kg) or L-694,247 (5-HT_1D agonist; 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-HT_1A ), CGS-12066B (5-HT_1B ), BRL 54443 (5-HT_1e/1F ), α-methyl-5-HT (5-HT₂ ), 1-PBG (5-HT₃ ), cisapride (5-HT₄ ) or AS-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-HT_1D receptor antagonist, LY310762 (1 mg/kg, i.v.), completely abolished L-694,247- and 5-HT-induced mesenteric sympathoinhibition. Furthermore, ELISA analysis confirmed 5-HT_1D receptors expression in mesenteric artery. These findings suggest that serotonergic mechanisms-induced sympathoinhibition of mesenteric noradrenergic outflow is mediated by pre and/or postjunctional 5-HT_1D receptors.

Keywords: 5-HT1D receptor; mesentery; sympathetic outflow; vascular.