Regional haemodynamic effects of the novel AT1 receptor antagonist, CV-11974, in conscious rats. 1994

R E Widdop, and X C Li, and B Jarrott
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.

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.

UI MeSH Term Description Entries
D006977 Hypertension, Renal Persistent high BLOOD PRESSURE due to KIDNEY DISEASES, such as those involving the renal parenchyma, the renal vasculature, or tumors that secrete RENIN. Hypertensions, Renal,Renal Hypertension,Renal Hypertensions
D008297 Male Males
D011918 Rats, Inbred SHR A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke. Rats, Spontaneously Hypertensive,Rats, SHR,Inbred SHR Rat,Inbred SHR Rats,Rat, Inbred SHR,Rat, SHR,Rat, Spontaneously Hypertensive,SHR Rat,SHR Rat, Inbred,SHR Rats,SHR Rats, Inbred,Spontaneously Hypertensive Rat,Spontaneously Hypertensive Rats
D011921 Rats, Inbred WKY A strain of Rattus norvegicus used as a normotensive control for the spontaneous hypertensive rats (SHR). Rats, Wistar Kyoto,Wistar Kyoto Rat,Rats, WKY,Inbred WKY Rat,Inbred WKY Rats,Kyoto Rat, Wistar,Rat, Inbred WKY,Rat, WKY,Rat, Wistar Kyoto,WKY Rat,WKY Rat, Inbred,WKY Rats,WKY Rats, Inbred,Wistar Kyoto Rats
D012039 Regional Blood Flow The flow of BLOOD through or around an organ or region of the body. Blood Flow, Regional,Blood Flows, Regional,Flow, Regional Blood,Flows, Regional Blood,Regional Blood Flows
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D003243 Consciousness Sense of awareness of self and of the environment. Consciousnesses
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001562 Benzimidazoles Compounds with a BENZENE fused to IMIDAZOLES.

Related Publications

R E Widdop, and X C Li, and B Jarrott
January 1997, European journal of pharmacology,
R E Widdop, and X C Li, and B Jarrott
January 1994, Blood pressure. Supplement,
R E Widdop, and X C Li, and B Jarrott
April 1994, Clinical and experimental pharmacology & physiology,
R E Widdop, and X C Li, and B Jarrott
July 1995, Journal of hypertension,
R E Widdop, and X C Li, and B Jarrott
April 2002, British journal of pharmacology,
R E Widdop, and X C Li, and B Jarrott
February 1997, Journal of autonomic pharmacology,
Copied contents to your clipboard!