Differential regional haemodynamic effects of the non-peptide angiotensin II antagonist, DuP 753, in water-replete and water-deprived Brattleboro rats.
Regional haemodynamic effects of DuP 753 were assessed in conscious unrestrained Brattleboro (i.e. vasopressin-deficient) rats, chronically instrumented with miniaturised pulsed Doppler flow probes and intravascular catheters. Responses to DuP 753 were assessed in water-replete animals and in animals following 14h water deprivation to render cardiovascular status dependent on the renin angiotensin system (RAS). In water-replete animals DuP 753 had little effect on mean arterial blood pressure, but there were dose-dependent tachycardias and increases in renal blood flow, associated with vasodilatations. There were also increases in mesenteric blood flow and vascular conductance, but these were not clearly dose-related; DuP 753 had no significant effects on hindquarters haemodynamics. In water-deprived animals DuP 753 caused dose-dependent hypotension, tachycardia, and renal and mesenteric vasodilatations; hindquarters vasodilatation was not dose-dependent. In both conditions, in the presence of DuP 753 (10 mg/kg), captopril had little additional effect. DuP 753 appears to be an extremely effective tool for assessing the role of the RAS in cardiovascular regulation.
Batin
P
P
Department of Medicine, Queen's Medical Centre, Nottingham, UK.
Gardiner
S M
SM
Compton
A M
AM
Bennett
T
T
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004326:Drinking; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D007866:Leg / Q000098:blood supply; D019808:Losartan; D008297:Male; D051381:Rats; D011910:Rats, Brattleboro; D012039:Regional Blood Flow / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D002216:Captopril; D019808:Losartan