title: Bolus injection of human UII in conscious rats evokes a biphasic haemodynamic response.
abstract: A biphasic cardiovascular response to bolus i.v. injection of human urotensin II (hUII, 3 nmol kg(-1)) in conscious, male, Sprague-Dawley (SD) rats was identified and underlying mechanisms were explored. Initially (0-5 min) there was tachycardia, hypotension and mesenteric and hindquarters vasodilatation; later (30-120 min), tachycardia, hindquarters vasodilatation and a modest rise in blood pressure occurred. Pretreatment with indomethacin or N(G) nitro-l-arginine methylester (l-NAME) reduced the mesenteric vasodilator response to hUII, and abolished the late tachycardia and hindquarters vasodilatation. Indomethacin also abolished the hypotension and early hindquarters vasodilatation, and substantially reduced the initial tachycardia. Indomethacin and l-NAME together prevented all haemodynamic responses to hUII. Inhibition of inducible NOS had no effect on responses to hUII, whereas inhibition of neuronal NOS reduced the delayed tachycardic response to hUII but did not significantly affect the vasodilatation. Only the initial tachycardic response to hUII was antagonised by propranolol. In spontaneously hypertensive rats (SHR), the initial haemodynamic responses to hUII were qualitatively similar to those in SD rats, although there was also a modest renal vasodilatation. The secondary response comprised a smaller tachycardia and a small rise in blood pressure, with no significant hindquarters vasodilatation. Haemodynamic responses to hUII were not enhanced by endothelin and angiotensin receptor antagonism in either SD rats or in SHRs. One interpretation of these results is that the primary response to bolus injection of hUII is prostanoid- or prostanoid- and NO-mediated (mesenteric vasodilatation) and that this triggers secondary events, which are dependent on eNOS (hindquarters vasodilatation) and neuronal NOS (tachycardia).
authors.affiliation: Centre for Integrated Systems Biology & Medicine, School of Biomedical Sciences, University of Nottingham, Nottingham. 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: Terence
authors.initials: T
authors.lastname: Bennett
mesh_terms: D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D003243:Consciousness; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007189:Indans / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D014579:Urotensins / Q000008:administration & dosage / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000578:Amidines; D001596:Benzylamines; D004791:Enzyme Inhibitors; D007189:Indans; C109599:N(omega)-propylarginine; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D014579:Urotensins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-; D001127:Arginine Vasopressin; C029677:urotensin II; D001120:Arginine; D011433:Propranolol; D019001:Nitric Oxide Synthase; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin