Endothelium-dependent relaxation of porcine pulmonary arteries via 5-HT1C-like receptors.
In PGF2 alpha-precontracted pulmonary arteries with intact endothelium, 5-hydroxytryptamine (5-HT, 1.0-100 nmol/l) caused a concentration-dependent reversible relaxation, at higher concentrations the contractile response prevailed. In endothelium-denuded vessels relaxation was absent. 5-HT-induced relaxation of precontracted pulmonary arteries was probably mediated by release of an endothelium-derived relaxing factor (EDRF). Preincubation of the arteries with methylene blue or NG-nitro-L-arginine (200 mumol/l) attenuated the relaxant effect. The 5-HT-induced relaxation was accompanied by an increase in cGMP. Indomethacin (3 mumol/l) did not influence the 5-HT-induced relaxation indicating that eicosanoids are not involved in the relaxant response to 5-HT. The 5-HT1C and 5-HT2 receptor agonist alpha-methyl-5-HT was as potent as 5-HT in inducing relaxation. The rank order of relaxant potency of the agonists investigated was alpha-methyl-5-HT > 5-HT > 5-methoxytryptamine > tryptamine > omega-methyl-5-HT > 5-carboxamidotryptamine > 2-methyl-5-HT > 5,6-dihydroxytryptamine > m-chlorophenylpiperazine > sumatriptan > 8-OH-DPAT. Phentolamine, pindolol and ICS 205-930 did not interfere with the relaxant effect. The 5-HT2 receptor antagonist ketanserin (1 mumol/l) inhibited the contractile response but did not alter vasodilatation. Apart from the blockade of the contractile effects, mesulergine, cyproheptadine and mianserin (0.1-3.0 mumol/l, each) induced a parallel shift to the right of the concentration-response curve for the relaxation induced by alpha-methyl-5-HT or 5-HT. Spiperone (0.3 mumol/l) exerted weak inhibitory effects on relaxation and contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Institut für Pharmakologie und Toxikologie, Medizinische Hochschule Erfurt, Federal Republic of Germany.
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D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D006152:Cyclic GMP; D007213:Indomethacin