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Contractile responses to human urotensin‐II in rat and human pulmonary arteries: effect of endothelial factors and chronic hypoxia in the rat
Author(s) -
MacLean M R,
Alexander D,
Stirrat A,
Gallagher M,
Douglas S A,
Ohlstein E H,
Morecroft I,
Polland K
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703314
Subject(s) - hypoxia (environmental) , pulmonary hypertension , medicine , endothelin 1 , endocrinology , pulmonary artery , contraction (grammar) , vasodilation , urotensin ii , nitric oxide , endothelin receptor , circulatory system , chemistry , receptor , oxygen , organic chemistry
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 ∼4 fold more potent than endothelin‐1 [ET‐1] ( P <0.01), although its E max was considerably less (∼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‐1 ( P <0.01). E max was enhanced ∼1.5 fold in the presence of N ω ‐nitro‐ L ‐arginine methylester ( L ‐NAME, 100 μ M , P <0.01) and ∼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 (∼250 μm 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. British Journal of Pharmacology (2000) 130 , 201–204; doi: 10.1038/sj.bjp.0703314