Widdop R E, Li X C, Jarrott B
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Blood Press Suppl. 1994;5:15-20.
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.
CV - 11974是一种新开发的血管紧张素II（AII）1型（AT1）受体拮抗剂，可降低多种高血压动物模型的平均动脉压（MAP）。本研究的目的是在清醒、长期植入仪器的自发性高血压大鼠（SHR）和肾性高血压2肾1夹（2K1C）大鼠以及相应的正常血压Wistar Kyoto大鼠和假手术大鼠中，研究CV - 11974对区域血流动力学的影响，这些影响有助于其降压作用。在SHR中，CV - 11974（0.1mg/kg，静脉注射）降低了MAP，增加了肾血流量和血管传导性，表明肾血管扩张。然而，肠系膜或后肢血管床的血流变化极小。相比之下，在2K1C大鼠中，CV - 11974引起显著低血压，且与所有三个血管床的显著血管扩张有关。外源性AII的心血管效应也被CV - 11974阻断。这些结果表明，尽管静息MAP相似，但在两种高血压大鼠模型中，CV - 11974的血流动力学特征存在细微差异，因为该化合物在SHR中引起相对选择性的肾血管扩张，而在2K1C大鼠中引起更广泛的血管扩张。
