Central losartan administration increases cardiac workload during aerobic exercise.

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.

Central angiotensin-(1-7) improves vagal function independent of blood pressure in hypertensive (mRen2)27 rats.

Hypertensive transgenic (mRen2)27 rats with overexpression of the mRen2 gene have impaired baroreflex sensitivity for heart rate control and high nicotinamide adenine dinucleotide phosphate oxidase and kinase-to-phosphatase signaling activity in medullary tissue compared with normotensive Hannover Sprague-Dawley control rats. They also exhibit insulin resistance at a young age. To determine whether blocking angiotensin II actions, supplementing angiotensin-(1-7), or scavenging reactive oxygen species in brain differentially alters mean arterial pressure, baroreflex sensitivity, or metabolic function, while altering medullary signaling pathways in these animals, we compared intracerebroventricular infusions of the angiotensin II type 1 receptor antagonist candesartan (4 µg/5 µL/h), angiotensin-(1-7) (0.1 µg/5 µL/h), a reactive oxygen species scavenger tempol (25 µg/5 µL/h), or artificial cerebrospinal fluid (5 µL/h) for 2 weeks. Mean arterial pressure was reduced in candesartan-treated rats without significantly improving the vagal components of baroreflex function or heart rate variability. In contrast, angiotensin-(1-7) treatment significantly improved the vagal components of baroreflex function and heart rate variability at a dose that did not significantly lower mean arterial pressure. Tempol significantly reduced nicotinamide adenine dinucleotide phosphate oxidase activity in brain dorsal medullary tissue but had no effect on mean arterial pressure or autonomic function. Candesartan tended to reduce fat mass, but none of the treatments significantly altered indices of metabolic function or mitogen-activated protein kinase signaling pathways in dorsal medulla. Although additional dose response studies are necessary to determine the potential maximal effectiveness of each treatment, the current findings demonstrate that blood pressure and baroreflex function can be essentially normalized independently of medullary nicotinamide adenine dinucleotide phosphate oxidase or mitogen-activated protein kinase in hypertensive (mRen2)27 rats.

Sinoaortic denervation prevents enhanced heat loss induced by central cholinergic stimulation during physical exercise.

The present study investigated whether the effects of central cholinergic stimulation on thermoregulation during exercise are modulated by arterial baroreceptors. Wistar rats were submitted to sinoaortic denervation (SAD) or sham denervation (SHAM) and then fitted with a chronic guide cannula into the lateral cerebral ventricle. After 2 weeks, a catheter was implanted into the ascending aorta, and a temperature sensor was implanted into the peritoneal cavity. Two days later, the rats were submitted to exercise on a treadmill at 18 m/min until fatigued. Thermoregulatory and cardiovascular responses were measured after injection of 2 µL of 10mM physostigmine (Phy) or 0.15M NaCl solution (Sal) into the cerebral ventricle. In SHAM rats, Phy injection induced a greater exercise-induced increase in blood pressure and lower increase in heart rate than Sal treatment. In the SAD group, the attenuation of heart rate in response to Phy was blocked despite an exaggerated increase in blood pressure. SHAM rats treated with Phy had a higher increase in tail skin temperature compared to Sal injection (31.9 ± 0.4 °C Phy-SHAM vs. 30.1 ± 0.6 °C Sal-SHAM, 5 min after injection; p<0.05), resulting in a lower exercise-induced increase in core temperature. In contrast, SAD blocked the Phy injection effects in thermoregulatory responses during exercise (tail temperature: 30.1 ± 1.2 °C Phy-SAD vs. 29.5 ± 1.2 °C Sal-SAD, 5 min, p = 0.65). Therefore, we conclude that the enhancement of cutaneous heat loss induced by central cholinergic stimulation during exercise is mediated primarily by arterial baroreceptors.