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-HT(1D) receptor agonist sumatriptan were studied in isolated bovine pulmonary artery rings. The effects of the antagonists, ketanserin (5-HT(2A)-receptors) and methiothepin (5-HT1- and 5-HT(2A)-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(ω)-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-HT(1D) 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. The results indicate that, in bovine pulmonary arteries, in the absence of vascular tone, 5-HT mediates vasoconstriction via 5-HT(2A) receptors whilst with tone present, a 5-HT(1D)-like response to both 5-HT and sumatriptan is observed. The sumatriptan-induced response is potentiated by L-NAME and endothelium removal. © 1994 Academic Press.