Effects of Angiotensin II Receptor Blockade During Exercise: Comparison of Losartan and Saralasin

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Abstract
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.