5-HT1-receptor-mediated vasoconstriction in bovine isolated pulmonary arteries: influences of vascular endothelium and tone

Pulm Pharmacol. 1994 Feb;7(1):65-72. doi: 10.1006/pulp.1994.1007.

Abstract

Vasoconstrictor responses to 5-hydroxytryptamine (5-HT) and the 5-HT1D receptor agonist sumatriptan were studied in isolated bovine pulmonary artery rings. The effects of the antagonists, ketanserin (5-HT2A-receptors) and methiothepin (5-HT1- and 5-HT2A-receptors) on these responses were determined. The influences of vascular tone and the effect of removal of the vascular endothelium and pretreatment with the inhibitor of nitric oxide synthase, N omega-nitro-L-arginine methylester, were also studied. In the absence of tone, in the majority of vessels, sumatriptan did not induce significant contractions. 5-HT-induced responses were concentration-dependent and ketanserin and methiothepin antagonized these in a competitive fashion. Removal of the endothelium or inclusion of L-NAME potentiated responses to sumatriptan. The sensitivity to sumatriptan was increased by L-NAME only in the presence of the endothelium whilst maximum responses to sumatriptan were potentiated in both unrubbed and rubbed vessels. Removal of the endothelium and/or inclusion of L-NAME had no significant effect on responses to 5-HT. U46619-induced tone markedly increased sumatriptan-induced responses which were competitively antagonized by methiothepin but were relatively resistant to ketanserin, verifying activation of a 5-HT1D receptor. Responses to 5-HT were also potentiated and competitively antagonized by ketanserin, and further antagonized by methiothepin. With tone present, lower concentrations of 5-HT were ketanserin-resistant and methiothepin-sensitive, indicating activation of a 5-HT1-like receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Cattle
  • Drug Interactions
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • In Vitro Techniques
  • Ketanserin / pharmacology
  • Methiothepin / pharmacology
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology*
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide Synthase
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / physiology*
  • Receptors, Serotonin / physiology*
  • Sensitivity and Specificity
  • Serotonin / pharmacology
  • Serotonin Antagonists
  • Sumatriptan / pharmacology
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology*

Substances

  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin
  • Methiothepin
  • Sumatriptan
  • Arginine
  • Ketanserin
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • NG-Nitroarginine Methyl Ester