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Pharmacological evidence that 5‐HT 1D activation induces renal vasodilation by NO pathway in rats
Author(s) -
GarcíaPedraza JoséÁngel,
García Mónica,
Martín MaríaLuisa,
Morán Asunción
Publication year - 2015
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 - 10.1111/1440-1681.12397
Subject(s) - vasodilation , ritanserin , phenylephrine , medicine , agonist , endocrinology , chemistry , kidney , antagonist , vasoconstriction , blood pressure , pharmacology , receptor antagonist , receptor
Summary 5‐HT is a powerful vasoconstrictor substance in renal vasculature (mainly by 5‐HT 2 activation). Nevertheless, 5‐HT is notable for its dual cardiovascular effects, producing both vasodilator and vasoconstrictor actions. This study aimed to investigate whether, behind the predominant serotonergic vasoconstrictor action, THE 5‐HT system may exert renal vasodilator actions, and, if so, characterize the 5‐HT receptors and possible indirect pathways. Renal perfusion pressure ( PP ), systemic blood pressure ( SBP ) and heart rate ( HR ) measurement in in situ autoperfused rat kidney was determined in phenylephrine infused rats. Intra arterial (i.a.) bolus administration of 5‐HT (0.125–0.1 μg/kg) decreased renal PP in the presence of a phenylephrine continuous infusion (phenylephrine‐infusion group), without modifying SBP or HR . These vasodilator responses were potentiated by 5‐HT 2 antagonism (ritanserin, 1 mg/kg i.v.), whereas the responses were abolished by 5‐HT 1/7 antagonist (methiothepin, 100 μg/kg i.v.) or 5‐HT 1D antagonist (LY310762, 1 mg/kg i.v.). The i.a. administration (0.125 to 0.1 μg/kg) of 5‐CT or L‐694,247 (5‐HT 1D agonist) mimicked 5‐HT vasodilator effect, while other agonists (1‐PBG, α ‐methyl‐5‐HT, AS‐19 (5‐HT 7 ), 8‐OH‐DPAT (5‐HT 1A ) or CGS‐12066B (5‐HT 1B )) did not alter baseline haemodynamic variables. L‐694,247 vasodilation was abolished by i.v. bolus of antagonists LY310762 (5‐HT 1D , 1 mg/kg) or L‐NAME (nitric oxide, 10 mg/kg), but not by i.v. bolus of indomethacin (cyclooxygenase, 2 mg/kg) or glibenclamide (ATP‐dependent K + channel, 20 mg/kg). These outcomes suggest that 5‐HT 1D activation produces a vasodilator effect in the in situ autoperfused kidney of phenylephrine‐infusion rats mediated by the NO pathway.