COMPARISON OF THE EFFECT OF ENDOTHELIUM ON THE RESPONSES TO SUMATRIPTAN IN RABBIT ISOLATED ILIAC, MESENTERIC AND CAROTID ARTERIES

The contractions induced by the 5-hydroxytryptamine (5-HT) and 5-HT1-l ike 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 inve stigated. 5-HT induced concentration-dependent contractions of all the se 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 F-2 alpha, i t elicited contractions of both arteries (E(max) values for sumatripta n in mesenteric and iliac arteries were 84.7% and 29.7% of the phenyle phrine maximal effect and EC(50) values were 0.22 +/- 0.14 and 0.33 +/ - 0.06 mu M, respectively). Sumatriptan had no contractile effect at a ll in carotid arteries in which 5-HT-induced contractions seemed to be mediated by 5-HT, receptors only.Removal of the endothelium did not a ffect the responses to 5-HT in iliac, mesenteric and carotid arteries. The contractions induced by sumatriptan were not influenced by remova l of the endothelium in the mesenteric artery, while sumatriptan respo nses were potentiated in the endothelium-denuded preparations of the i liac artery (E(max) = 50.8% of the phenylphrine maximal effect; EC(50) = 0.46 mu M). L-N-G-monomethyl arginine (100 mu M), a nitric oxide sy nthase inhibitor, also potentiated the sumatriptan responses in the en dothelium-intact segments of the iliac artery. Indomethacin (0.1 mu M) , a cyclooxygenase inhibitor, did not affect the sumatriptan responses . These results suggest that sumatriptan-induced contractions of the r abbit iliac, but not mesenteric artery, were depressed by itself throu gh the release of nitric oxide upon stimulation of 5-HT1-like receptor s located on the endothelium, whereas neither on vascular smooth muscl e nor on endothelium, 5-HT1-like receptors were present in the rabbit carotid artery.