Pharmacological evidence that 5-HT1D activation induces renal vasodilation by NO pathway in rats

Clin Exp Pharmacol Physiol. 2015 Jun;42(6):640-7. doi: 10.1111/1440-1681.12397.

Abstract

5-HT is a powerful vasoconstrictor substance in renal vasculature (mainly by 5-HT₂ 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-HT₂ antagonism (ritanserin, 1 mg/kg i.v.), whereas the responses were abolished by 5-HT₁ /₇ antagonist (methiothepin, 100 μg/kg i.v.) or 5-HT1D 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-HT1D agonist) mimicked 5-HT vasodilator effect, while other agonists (1-PBG, α-methyl-5-HT, AS-19 (5-HT₇), 8-OH-DPAT (5-HT1A) or CGS-12066B (5-HT1B)) did not alter baseline haemodynamic variables. L-694,247 vasodilation was abolished by i.v. bolus of antagonists LY310762 (5-HT1D, 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-HT1D activation produces a vasodilator effect in the in situ autoperfused kidney of phenylephrine-infusion rats mediated by the NO pathway.

Keywords: 5-HT1D receptor; 5-hydroxytryptamine; autoperfused rat kidney; nitric oxide; renal vasodilation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Kidney / blood supply
  • Kidney / drug effects
  • Kidney / physiology*
  • Male
  • Nitric Oxide / physiology*
  • Phenylephrine / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1D / metabolism*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology*
  • Vasodilation / drug effects
  • Vasodilation / physiology*

Substances

  • Receptor, Serotonin, 5-HT1D
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Phenylephrine
  • Nitric Oxide