Comparison of the effect of endothelium on the responses to sumatriptan in rabbit isolated iliac, mesenteric and carotid arteries.

Abstract

The contractions induced by the 5-hydroxytryptamine (5-HT) and 5-HT1-like receptor agonist sumatriptan in open ring segments of rabbit iliac, mesenteric and common carotid arteries were studied isometrically in vitro. The alteration of the responses by removal of the endothelium and by inhibitors of nitric oxide synthase and cyclooxygenase was investigated. 5-HT induced concentration-dependent contractions of all these three arterial segments. Sumatriptan did not induce any contraction of quiescent mesenteric and iliac arteries, but when a moderate tone was given with a threshold concentration of prostaglandin F2 alpha, it elicited contractions of both arteries (Emax values for sumatriptan in mesenteric and iliac arteries were 84.7% and 29.7% of the phenylephrine maximal effect and EC50 values were 0.22 +/- 0.14 and 0.33 +/- 0.06 microM, respectively). Sumatriptan had no contractile effect at all in carotid arteries in which 5-HT-induced contractions seemed to be mediated by 5-HT2 receptors only. Removal of the endothelium did not affect the responses to 5-HT in iliac, mesenteric and carotid arteries. The contractions induced by sumatriptan were not influenced by removal of the endothelium in the mesenteric artery, while sumatriptan responses were potentiated in the endothelium-denuded preparations of the iliac artery (Emax = 50.8% of the phenylphrine maximal effect; EC50 = 0.46 microM). L-NG-monomethyl arginine (100 microM), a nitric oxide synthase inhibitor, also potentiated the sumatriptan responses in the endothelium-intact segments of the iliac artery. Indomethacin (0.1 microM), a cyclooxygenase inhibitor, did not affect the sumatriptan responses. These results suggest that sumatriptan-induced contractions of the rabbit iliac, but not mesenteric artery, were depressed by itself through the release of nitric oxide upon stimulation of 5-HT1-like receptors located on the endothelium, whereas neither on vascular smooth muscle nor on endothelium, 5-HT1-like receptors were present in the rabbit carotid artery.