Contractile responses to human urotensin-II in rat and human pulmonary arteries: effect of endothelial factors and chronic hypoxia in the rat

Responses to human urotensin-II (hU-II) were investigated in human and rat pulmonary arteries. Rat pulmonary arteries: hU-II was a potent vasoconstric tor of main pulmonary arteries (2-3 mm i.d.) (pEC(50), 8.55 +/- 0.08, n = 2 1) and was similar to 4 fold more potent than endothelin-l [ET-I] (P < 0.01 ), although its E-max was considerably less (similar to 2.5 fold, P < 0.001 ). The potency of hU-II increased 2.5 fold with endothelium removal(P < 0.0 5) and after raising vascular tone with ET-I (P < 0.01). E-max was enhanced similar to 1.5 fold in the presence of N-omega-nitro-L-arginine methyleste r (L-NAME, 100 mu M, P < 0.01) and similar to 2 fold in vessels from pulmon ary hypertensive rats exposed to 2 weeks chronic hypoxia (P < 0.05). hU-II did not constrict smaller pulmonary arteries. Human pulmonary arteries (sim ilar to 250 mu m i.d.): in the presence of L-NAME, 3 out of 10 vessels cont racted to hU-II and this contraction was highly variable. hU-II is, therefo re, a potent vasoconstrictor of rat main pulmonary arteries and this respon se is increased by endothelial factors, vascular tone and onset of pulmonar y hypertension. Inhibition of nitric oxide synthase uncovers contractile re sponses to hU-II in human pulmonary arteries.