EFFECTS OF ANGIOTENSIN-II RECEPTOR BLOCKADE DURING EXERCISE - COMPARISON OF LOSARTAN AND SARALASIN

Previous studies indicate that angiotensin II (ANG II) plays a minor r ole in the hemodynamic responses during dynamic exercise. However, non specific 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 nonspecif ic effects. We hypothesized that the contribution of ANG II to the car diovascular response to dynamic exercise is characterized more precise ly with losartan than with saralasin. On separate days, 6 miniswine pe rformed treadmill running at 80% of their maximal heart rate (HR) rese rve (HRR) in the presence of vehicle (0.9% saline), saralasin (10 or 2 0 mu g/kg/min intraleft arterially, i.a.), or losartan (15 or 20 mg/kg i.a.). Cardiac output (GO), HR, and myocardial contractility were sim ilar among all exercise conditions. As compared with the vehicle, losa rtan decreased mean arterial pressure (MAP) and systemic vascular resi stance (SVR) during exercise, whereas no differences occurred between the vehicle and saralasin conditions. Both receptor antagonists increa sed 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 conclu de that the contribution of ANG II to the cardiovascular response to d ynamic exercise is demonstrated more clearly with losartan than with s aralasin.