Central losartan administration increases cardiac workload during aerobic exercise

Abstract

To assess the effects of central administration of losartan, an antagonist of angiotensin II AT1 receptors, on cardiovascular function during aerobic exercise, heart rate, systolic and diastolic arterial pressures and rate pressure product of Wistar rats were measured as cardiac workload indexes. The animals ran on a treadmill until fatigue after an intracerebroventricular injection of losartan or saline. Pulsatile arterial pressure was recorded by a catheter implanted into the ascending aorta, from which were derived cardiovascular parameters to estimate the cardiac workload. Total exercise time and exercise workload were determined as performance indexes. The rats showed a more intense increase in heart rate after 8 min of exercise and sustained until fatigue (P < .05). Furthermore, the rats injected with losartan had a higher increase of both systolic and diastolic arterial pressures as well as rate pressure product from approximately 6 min of exercise until fatigued (P < .05). In addition, a 22% reduction in exercise time was found in losartan-rats (P < .01). This ergolytic effect induced by losartan was strongly inversely correlated with rate-pressure product during aerobic exercise (r = 0.78, P ≤ .01). The data shows that central administration of losartan augments the cardiac workload during aerobic exercise, which courses in parallel with the reduced exercise performance.