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Human urotensin‐II is an endothelium‐dependent vasodilator in rat small arteries
Author(s) -
Bottrill Fiona E,
Douglas Stephen A,
Hiley C Robin,
White Richard
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.0703513
Subject(s) - endothelium , vasodilation , contraction (grammar) , urotensin ii , medicine , mesenteric arteries , endocrinology , methoxamine , aorta , circulatory system , artery , blood vessel , endothelium derived relaxing factor , basilar artery , anatomy , agonist , receptor
The possible role of the endothelium in modulating responses to human urotensin‐II (U‐II) was investigated using isolated segments of rat thoracic aorta, small mesenteric artery, left anterior descending coronary artery and basilar artery. Human U‐II was a potent vasoconstrictor of endothelium‐intact isolated rat thoracic aorta (EC 50 =3.5±1.1 n M , R max =103±10% of control contraction induced by 60 m M KCl and 1 μ M noradrenaline). However the contractile response was not significantly altered by removal of the endothelium or inhibition of nitric oxide synthesis with L ‐NAME (100 μ M ). Human U‐II did not cause relaxation of noradrenaline‐precontracted, endothelium‐intact rat aortae. Human U‐II contracted endothelium‐intact rat isolated left anterior descending coronary arteries (EC 50 =1.3±0.8 n M , R max =20.1±4.9% of control contraction induced by 10 μ M 5‐HT). The contractile response was significantly enhanced by removal of the endothelium (R max =55.4±16.1%). Moreover, human U‐II caused concentration‐dependent relaxation of 5‐HT‐precontracted arteries, which was abolished by L ‐NAME or removal of the endothelium. No contractile effects of human U‐II were found in rat small mesenteric arteries. However the peptide caused potent, concentration‐ and endothelium‐dependent relaxations of methoxamine‐precontracted vessels. The relaxant responses were potentiated by L ‐NAME (300 μ M ) but abolished in the additional presence of 25 m M KCl (which inhibits the actions of endothelium‐derived hyperpolarizing factor). The present study is the first to show that human U‐II is a potent endothelium‐dependent vasodilator in some rat resistance vessels, and acts through release of EDHF as well as nitric oxide. Our findings have also highlighted clear anatomical differences in the responses of different vascular beds to human U‐II which are likely to be important in determining the overall cardiovascular activity of this peptide.British Journal of Pharmacology (2000) 130 , 1865–1870; doi: 10.1038/sj.bjp.0703513