Cody R J, Binkley P F, Haas G J, Brown D M
Department of Medicine, Ohio State University Medical Center, Columbus 43210, USA.
Am J Hypertens. 1995 May;8(5 Pt 1):500-8. doi: 10.1016/0895-7061(95)00019-L.
As the AT1 receptor is the primary angiotensin II receptor in the myocardium and vasculature, we assessed the acute myocardial and vascular response to the AT1 angiotensin II antagonist losartan in the spontaneously hypertensive rat (SHR) to determine the contribution of angiotensin II in this genetic form of hypertension. In a preliminary dose response study, which evaluated losartan at 1.0, 3.0, and 10 mg/kg, 10 mg/kg uniformly lowered blood pressure. In a second group of experiments, 10 mg/kg also completely attenuated the pressor effects of angiotensin II administration. In nine adult SHR, intravenous losartan, 10 mg/kg, was given, with hemodynamics measured immediately and at steady-state intervals to delineate the hemodynamic response to angiotensin II antagonism. Losartan significantly lowered systolic, diastolic, and mean blood pressures, yet heart rate was unchanged. Cardiac function, as assessed by cardiac output and blood flow acceleration, demonstrated only transient increases which were not sustained during steady-state blood pressure reduction. Significant increases of peak blood flow and pulse pressure were sustained throughout the blood pressure response. At immediate and steady-state determinations, system vascular resistance and characteristic aortic impedance were significantly reduced with losartan (both P < .01). In addition, concomitant reduction of the wave reflectance index also occurred, achieving significance at steady state (P < .05). These changes demonstrate that the AT1 angiotensin II receptor contributes to both central and peripheral vasoconstriction in the spontaneously hypertensive rat. Absence of sustained increase of cardiac output and blood flow acceleration are consistent with inhibition of the previously reported positive inotropic effect of angiotensin II.
由于AT1受体是心肌和血管系统中的主要血管紧张素II受体，我们评估了自发性高血压大鼠（SHR）对AT1血管紧张素II拮抗剂氯沙坦的急性心肌和血管反应，以确定血管紧张素II在这种遗传性高血压中的作用。在一项初步剂量反应研究中，评估了氯沙坦1.0、3.0和10mg/kg的剂量，10mg/kg能均匀降低血压。在第二组实验中，10mg/kg也完全减弱了血管紧张素II给药的升压作用。在9只成年SHR中，静脉注射10mg/kg氯沙坦，立即和在稳态间隔测量血流动力学，以描绘对血管紧张素II拮抗作用的血流动力学反应。氯沙坦显著降低收缩压、舒张压和平均血压，但心率不变。通过心输出量和血流加速评估的心脏功能仅表现出短暂增加，在稳态血压降低期间未持续。在整个血压反应过程中，峰值血流和脉压持续显著增加。在即时和稳态测定时，氯沙坦使系统血管阻力和特征性主动脉阻抗显著降低（均P <.01）。此外，波反射指数也随之降低，在稳态时达到显著水平（P <.05）。这些变化表明，AT1血管紧张素II受体在自发性高血压大鼠的中枢和外周血管收缩中均起作用。心输出量和血流加速未持续增加与抑制先前报道的血管紧张素II的正性肌力作用一致。
