title: Regional heterogeneity in the haemodynamic responses to urotensin II infusion in relation to UT receptor localisation.
abstract: The aim of the study was to measure regional haemodynamic responses to 6 h infusions of human urotensin II (hUII), to identify possible mediators of the effects observed, and to relate the findings to the distribution of urotensin II receptors (UT receptors). Male, Sprague-Dawley rats had pulsed Doppler flow probes and intravascular catheters implanted for measurement of regional haemodynamics in the conscious, freely moving state. Infusions of saline (0.4 ml h(-1)) or hUII (30, 300 and 3,000 pmol kg(-1) h(-1)) were given i.v. for 6 h, and the effects of pretreatment with indomethacin (5 mg kg(-1) h(-1)), N(G)-nitro-L-arginine methyl ester (L-NAME, 3 mg kg(-1) h(-1)) or propranolol (1 mg kg(-1); 0.5 mg kg(-1) h(-1)) on responses to hUII (300 pmol kg(-1) h(-1) for 6 h) were assessed. Cellular localisation of UT receptor-like immunoreactivity was determined in relevant tissues. hUII caused dose-dependent tachycardia and hindquarters vasodilatation, accompanied by a slowly developing rise in blood pressure. Haemodynamic effects of hUII were attenuated by propranolol or L-NAME and abolished by indomethacin. UT receptor-like immunoreactivity was detected in skeletal and vascular smooth muscle. The findings indicate that in conscious rats, infusions of hUII cause vasodilatation, which, of the vascular beds monitored, is selective for the hindquarters and dependent on cyclooxygenase products and nitric oxide. The pressor effect of hUII under these conditions is likely to be due to an increase in cardiac output, possibly due to a positive inotropic effect. UT receptor-like immunoreactivity present in skeletal muscle is consistent with the haemodynamic pattern.
authors.affiliation: Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH. sheila.gardiner@nottingham.ac.uk
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Gardiner
authors.forename: Julie E
authors.initials: JE
authors.lastname: March
authors.forename: Philip A
authors.initials: PA
authors.lastname: Kemp
authors.forename: Janet J
authors.initials: JJ
authors.lastname: Maguire
authors.forename: Rhoda E
authors.initials: RE
authors.lastname: Kuc
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Davenport
authors.forename: Terence
authors.initials: T
authors.lastname: Bennett
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects*; D006614:Hindlimb; D007213:Indomethacin / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism*; D012039:Regional Blood Flow; D014579:Urotensins / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation
chemical_list: D000319:Adrenergic beta-Antagonists; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; C473142:Uts2r protein, rat; C029677:urotensin II; D011433:Propranolol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin