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 vasoconstrictor of main pulmonary arteries (2-3 mm i.d.) (pEC(50), 8.55 +/- 0.08, n = 21) 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 < 0.05) 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 methylester (L-NAME, 100 mu M, P < 0.01) and similar to 2 fold in vessels from pulmonary hypertensive rats exposed to 2 weeks chronic hypoxia (P < 0.05). hU-II did not constrict smaller pulmonary arteries. Human pulmonary arteries (similar to 250 mu m i.d.): in the presence of L-NAME, 3 out of 10 vessels contracted to hU-II and this contraction was highly variable. hU-II is, therefore, a potent vasoconstrictor of rat main pulmonary arteries and this response is increased by endothelial factors, vascular tone and onset of pulmonary hypertension. Inhibition of nitric oxide synthase uncovers contractile responses to hU-II in human pulmonary arteries.