Effects of physical training on hypothalamic neuronal activation and expressions of vasopressin and oxytocin in SHR after running until fatigue.

To assess the influence of physical training on neuronal activation and hypothalamic expression of vasopressin and oxytocin in spontaneously hypertensive rats (SHR), untrained and trained normotensive rats and SHR were submitted to running until fatigue while internal body and tail temperatures were recorded. Hypothalamic c-Fos expression was evaluated in thermoregulatory centers such as the median preoptic nucleus (MnPO), medial preoptic nucleus (mPOA), paraventricular nucleus of the hypothalamus (PVN), and supraoptic nucleus (SON). The PVN and the SON were also investigated for vasopressin and oxytocin expressions. Although exercise training improved the workload performed by the animals, it was reduced in SHR and followed by increased internal body temperature due to tail vasodilation deficit. Physical training enhanced c-Fos expression in the MnPO, mPOA, and PVN of both strains, and these responses were attenuated in SHR. Vasopressin immunoreactivity in the PVN was also increased by physical training to a lesser extent in SHR. The already-reduced oxytocin expression in the PVN of SHR was increased in response to physical training. Within the SON, neuronal activation and the expressions of vasopressin and oxytocin were reduced by hypertension and unaffected by physical training. The data indicate that physical training counterbalances in part the negative effect of hypertension on hypothalamic neuronal activation elicited by exercise, as well as on the expression of vasopressin and oxytocin. These hypertension features seem to negatively influence the workload performed by SHR due to the hyperthermia derived from the inability of physical training to improve heat dissipation through skin vasodilation.

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.

The improvement of exercise performance by physical training is related to increased hypothalamic neuronal activation.

The effects of physical training on hypothalamic activation after exercise and their relationship with heat dissipation were investigated. Following 8 weeks of physical training, trained (TR, n = 9) and untrained (UN, n = 8) Wistar rats were submitted to a regimen of incremental running until fatigue while body and tail temperatures were recorded. After exercise, hypothalamic c-Fos immunohistochemistry analysis was performed. The workload, body-heating rate, heat storage and body temperature threshold for cutaneous vasodilation were calculated. Physical training increased the number of c-Fos immunoreactive neurons in the paraventricular, medial preoptic and median preoptic nucleus by 112%, 90% and 65% (P < 0.01) after exercise, respectively. In these hypothalamic regions, increased neuronal activation was directly associated with the increased workload performed by TR animals (P < 0.01). Moreover, a reduction of 0.6°C in the body temperature threshold for cutaneous vasodilation was shown by TR animals (P < 0.01). This reduction was possibly responsible for the lower body-heating rate (0.019 ± 0.002°C/min, TR vs 0.030 ± 0.005°C/min, UN, P < 0.05) and the decreased ratio between heat storage and the workload performed by TR animals (18.18 ± 1.65 cal/kg, TR vs 31.38 ± 5.35 cal/kg, UN, P < 0.05). The data indicate that physical training enhances hypothalamic neuronal activation during exercise. This enhancement is the central adaptation relating to better physical performance, characterized by a lower ratio of heat stored to workload performed, due to improved heat dissipation.

Central blockade of nitric oxide transmission impairs exercise-induced neuronal activation in the PVN and reduces physical performance.

The blockade of central nitric oxide (NO) signaling modifies the thermoregulatory and metabolic adjustments that occur during exercise, thereby impairing physical performance. However, the brain areas involved in this response remain unknown. Nitrergic neurons are present in the hypothalamic areas that are activated during exercise and participate in autonomic and neuroendocrine responses, such as, the hypothalamic paraventricular nucleus (PVN) and the supraoptic nucleus (SON). To investigate whether brain NO signaling affects thermoregulation during exercise through the activation of hypothalamic neurons, rats underwent acute submaximal treadmill exercise (18 mmin(-1), 5% inclination) until fatigue received an intracerebroventricular injection of 1.43 µmol Nω-nitro-l-arginine metil ester (L-NAME), a nitric oxide synthase inhibitor, or saline (SAL). Skin tail temperature (Tsk) and internal body temperature (Ti) were continuously recorded and c-Fos expression was determined in the PVN and the SON. L-NAME treatment reduced physical performance by 48%, which was positively correlated with tail vasodilation capacity, which was reduced by 28%, and negatively correlated with heat storage rate (HSR), which was increased by 38%. Physical exercise until fatigue increased the number of c-Fos-immunoreactive (ir) neurons in the PVN and the SON. L-NAME-treatment significantly reduced the exercise-induced c-Fos expression in the PVN, whereas it had no effect in the SON. Interestingly, the number of c-Fos-ir neurons in the PVN was closely correlated with physical performance and inversely associated with HSR. Thus, the inhibition of central NO attenuates neuronal activation induced by exercise in the PVN, impairs the autonomic regulation of heat dissipation, and anticipates the fatigue. Brain NO seems to play a role in exercise performance through the regulation of neuronal activation in the PVN, but not in the SON, although the SON neurons are also activated by running exercise. Moreover, this role in performance mediated by neuronal activation in the PVN can be related with the improvement of thermoregulatory adjustments that occur during exercise.

Implications of angiotensin II in central nervous system on exercise performance.

The renin-angiotensin system (RAS) consists of a complex enzyme-peptide system, which, besides from functioning as a circulating endocrine system, is also intrinsic in many organs and tissues, including the brain. Although the RAS generates a family of biological active peptides, angiotensin II (Ang II) is still considered one of its main mediators and effectors. Ang II produces many well defined and potent effects through AT1 and AT2 receptors and its physiological applications are yet expanding. Recently, it has been proposed that Ang II, acting both centrally and peripherally, interferes on exercise performance due to its influence on multiple functions within the organism. This hypothesis is also supported by evidences reporting an increased frequency of the ACE I allele among elite athletes, suggesting that this is a genetic factor that influences physical performance. The fatigue resulting from physical exercise is a multifactorial phenomenon that comprises the interaction between physiological factors of peripheral and/or central origin. To that extent, the Ang II-mediated events on factors that affect exercise performance such as cardiovascular, metabolic and thermoregulatory adjustments as well as cerebral metabolism and neurohumoral or neurotransmitter turnover, implicate the peptide in the genesis of exercise-induced fatigue. This mini-review focuses on how exercise-induced physiological adjustments are influenced by Ang II within the central nervous system and how these effects may limit athletic performance.