Potent vasodilator responses to human urotensin-II in human pulmonary and abdominal resistance arteries.
The peptide human urotensin-II (hUT-II) and its receptor have recently been cloned. The vascular function of this peptide in humans, however, has yet to be determined. Vasoconstrictor and vasodilator responses to hUT-II were investigated in human small muscular pulmonary arteries [approximately 70 microm internal diameter (ID)] and human abdominal resistance arteries (approximately 200 microm ID). Vasodilator responses were investigated in endothelin-1 (3 nM) precontracted vessels and, in the small pulmonary vessels, compared with the known vasodilators adrenomedullin, sodium nitroprusside, and acetylcholine. In human small pulmonary arteries, hUT-II did not induce vasoconstriction but was a potent vasodilator [-log M concentration causing 50% of the maximum vasodilator effect (pIC(50)) 10.4 +/- 0.5; percentage of reduction in tone (E(max)) 81 +/- 8% (vs. 23 +/- 11% in time controls), n = 5]. The order of potency for vasodilation was human urotensin-II = adrenomedullin (pIC(50) 10.1 +/- 0.4, n = 6) > sodium nitroprusside (pIC(50) 7.4 +/- 0.2, n = 6) = acetylcholine (pIC(50) 6.8 +/- 0.3, n = 6). In human abdominal arteries, hUT-II did not induce vasoconstriction but was a potent vasodilator [pIC(50) 10.3 +/- 0.7; E(max) 96 +/- 8% (vs. 43 +/- 16% in time controls), n = 4]. This is the first report that hUT-II is a potent vasodilator but not a vasoconstrictor of human small pulmonary arteries and systemic resistance arteries.
Stirrat
A
A
Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, Glasgow University, Glasgow G12 8QQ.
Gallagher
M
M
Douglas
S A
SA
Ohlstein
E H
EH
Berry
C
C
Kirk
A
A
Richardson
M
M
MacLean
M R
MR
D000005:Abdomen / Q000098:blood supply; D000109:Acetylcholine / Q000494:pharmacology; D053607:Adrenomedullin; D000328:Adult; D000368:Aged; D019332:Endothelin-1 / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D014579:Urotensins / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D019332:Endothelin-1; D010455:Peptides; D014579:Urotensins; D014665:Vasodilator Agents; D053607:Adrenomedullin; D009599:Nitroprusside; C029677:urotensin II; D000109:Acetylcholine