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 approximately 4 fold more potent than endothelin-1 [ET-1] (P<0.01), although its E(max) was considerably less (approximately 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 approximately 1.5 fold in the presence of N(omega)-nitro-L-arginine methylester (L-NAME, 100 microM, P<0.01) and approximately 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 ( approximately 250 microm 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.
MacLean
M R
MR
Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, Glasgow University, Glasgow G12 8QQ. United Kingdom. M.Maclean@bio.gla.ac.uk
Alexander
D
D
Stirrat
A
A
Gallagher
M
M
Douglas
S A
SA
Ohlstein
E H
EH
Morecroft
I
I
Polland
K
K
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016228:Endothelial Growth Factors; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology; D000860:Hypoxia; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010100:Oxygen / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014579:Urotensins / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D016228:Endothelial Growth Factors; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D014579:Urotensins; C029677:urotensin II; D019001:Nitric Oxide Synthase; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester