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Pharmacological evidence that 5-HT1D activation induces renal vasodilation by NO pathway in rats.
- Source :
- Clinical & Experimental Pharmacology & Physiology; Jun2015, Vol. 42 Issue 6, p640-647, 8p, 1 Diagram, 1 Chart, 5 Graphs
- Publication Year :
- 2015
-
Abstract
- 5-HT is a powerful vasoconstrictor substance in renal vasculature (mainly by 5-HT<subscript>2</subscript> 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 (0.00000125-0.1 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<subscript>2</subscript> antagonism (ritanserin, 1 mg/kg i.v.), whereas the responses were abolished by 5-HT<subscript>1/7</subscript> antagonist (methiothepin, 100 μg/kg i.v.) or 5-HT<subscript>1D</subscript> antagonist (LY310762, 1 mg/kg i.v.). The i.a. administration (0.00000125 to 0.1 μg/kg) of 5-CT or L-694,247 (5-HT<subscript>1D</subscript> agonist) mimicked 5-HT vasodilator effect, while other agonists (1-PBG, α-methyl-5-HT, AS-19 (5-HT<subscript>7</subscript>), 8-OH-DPAT (5-HT<subscript>1A</subscript>) or CGS-12066B (5-HT<subscript>1B</subscript>)) did not alter baseline haemodynamic variables. L-694,247 vasodilation was abolished by i.v. bolus of antagonists LY310762 (5-HT<subscript>1D</subscript>, 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<superscript>+</superscript> channel, 20 mg/kg). These outcomes suggest that 5-HT<subscript>1D</subscript> activation produces a vasodilator effect in the in situ autoperfused kidney of phenylephrine-infusion rats mediated by the NO pathway. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03051870
- Volume :
- 42
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Clinical & Experimental Pharmacology & Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 103031313
- Full Text :
- https://doi.org/10.1111/1440-1681.12397