5-HT1-receptor-mediated vasoconstriction in bovine isolated pulmonary arteries: influences of vascular endothelium and tone.
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)
MacLean
M R
MR
Institute of Physiology, University of Glasgow, UK.
Clayton
R A
RA
Hillis
S W
SW
McIntyre
P D
PD
Peacock
A J
AJ
Templeton
A G
AG
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002417:Cattle; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008719:Methiothepin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012680:Sensitivity and Specificity; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists; D018170:Sumatriptan / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D008719:Methiothepin; D018170:Sumatriptan; D001120:Arginine; D007650:Ketanserin; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester