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5‐ HT modulates the rat mesenteric vasopressor outflow by 5‐HT 1D sympatholytic receptors
Author(s) -
GarcíaPedraza JoséÁngel,
GarcíaDomingo Mónica,
GómezRoso Miriam,
RodríguezBarbero Alicia,
Martín MaríaLuisa,
Morán Asunción
Publication year - 2017
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12841
Subject(s) - endocrinology , agonist , ketanserin , medicine , serotonergic , mesenteric arteries , 5 ht receptor , receptor , hexamethonium , stimulation , serotonin , receptor antagonist , chemistry , antagonist , artery
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‐ 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‐ HT 2 ), 1‐ PBG (5‐ HT 3 ), cisapride (5‐ HT 4 ) or AS ‐19 (5‐ HT 7 ) (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, LY 310762 (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.