Symons J D, Stebbins C L
Department of Internal Medicine and Human Physiology, University of California, Davis 95616, USA.
J Cardiovasc Pharmacol. 1996 Aug;28(2):223-31. doi: 10.1097/00005344-199608000-00007.
Previous studies indicate that angiotensin II (ANG II) plays a minor role in the hemodynamic responses during dynamic exercise. However, nonspecific effects associated with methods used to block its production [e.g., angiotensin-converting enzyme (ACE) inhibitors] or receptors (e.g., saralasin) may have contributed to these findings. Losartan is a nonpeptide ANG II receptor antagonist that is devoid of such nonspecific effects. We hypothesized that the contribution of ANG II to the cardiovascular response to dynamic exercise is characterized more precisely with losartan than with saralasin. On separate days, 6 miniswine performed treadmill running at 80% of their maximal heart rate (HR) reserve (HRR) in the presence of vehicle (0.9% saline), saralasin (10 or 20 micrograms/kg/min intraleft arterially, i.a.), or losartan (15 or 20 mg/kg i.a.). Cardiac output (CO), HR, and myocardial contractility were similar among all exercise conditions. As compared with the vehicle, losartan decreased mean arterial pressure (MAP) and systemic vascular resistance (SVR) during exercise, whereas no differences occurred between the vehicle and saralasin conditions. Both receptor antagonists increased blood flow and/or decreased vascular resistance during exercise in the myocardium, stomach, small intestine, and colon. As compared with that during treadmill running with vehicle infusion, renal blood flow (RBF) was increased by losartan and decreased by saralasin. We conclude that the contribution of ANG II to the cardiovascular response to dynamic exercise is demonstrated more clearly with losartan than with saralasin.
先前的研究表明，血管紧张素II（ANG II）在动态运动期间的血流动力学反应中起次要作用。然而，与用于阻断其生成的方法[如血管紧张素转换酶（ACE）抑制剂]或受体（如沙拉新）相关的非特异性效应可能导致了这些研究结果。氯沙坦是一种非肽类ANG II受体拮抗剂，不存在此类非特异性效应。我们假设，与沙拉新相比，氯沙坦能更精确地表征ANG II对动态运动心血管反应的作用。在不同日期，6头小型猪在给予赋形剂（0.9%生理盐水）、沙拉新（10或20微克/千克/分钟经左动脉内注射，i.a.）或氯沙坦（15或20毫克/千克经动脉内注射，i.a.）的情况下，以其最大心率（HR）储备（HRR）的80%进行跑步机跑步。在所有运动条件下，心输出量（CO）、HR和心肌收缩力相似。与赋形剂相比，氯沙坦在运动期间降低了平均动脉压（MAP）和全身血管阻力（SVR），而赋形剂和沙拉新条件之间没有差异。两种受体拮抗剂在运动期间均增加了心肌、胃、小肠和结肠的血流量和/或降低了血管阻力。与输注赋形剂进行跑步机跑步时相比，氯沙坦增加了肾血流量（RBF），而沙拉新降低了肾血流量。我们得出结论，与沙拉新相比，氯沙坦能更清楚地证明ANG II对动态运动心血管反应的作用。
