Regional haemodynamic effects of the novel AT1 receptor antagonist, CV-11974, in conscious rats.
CV-11974, a newly developed angiotensin II (AII) subtype 1 (AT1) receptor antagonist, lowers mean arterial pressure (MAP) in various hypertensive animal models. The aim of this study was to examine the regional haemodynamic effects of CV-11974, which contribute to its hypotensive action, in conscious, chronically instrumented spontaneously hypertensive rats (SHR) and renal hypertensive 2-kidney, 1-clip (2K1C) rats, as well as in appropriate normotensive Wistar Kyoto and sham-operated rats. In SHR, CV-11974 (0.1 mg/kg, i.v.) lowered MAP and increased renal blood flow and conductance, indicating renal vasodilatation. However, there were minimal changes in blood flow in the mesenteric or hindquarters vascular beds. By contrast, in 2K1C rats, CV-11974 caused marked hypotension which was associated with substantial vasodilatation in all three vascular beds. The cardiovascular effects of exogenous AII were also blocked by CV-11974. These results suggest that there are subtle differences in the haemodynamic profile of CV-11974 in the two hypertensive rat models, despite similar resting MAP, since this compound caused a relatively selective renal vasodilatation in SHR, but more widespread vasodilatation in 2K1C rats.
Widdop
R E
RE
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Li
X C
XC
Jarrott
B
B
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness; D006439:Hemodynamics / Q000187:drug effects*; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan