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.

Plant-based diets benefit aerobic performance and do not compromise strength/power performance: a systematic review and meta-analysis.

Plant-based diets have emerged as athletic performance enhancers for various types of exercise. Therefore, the present study evaluated the effectiveness of plant-based diets on aerobic and strength/power performances, as well as on BMI of physically active individuals. This systematic review and meta-analysis was conducted and reported according to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. A systematic search of electronic databases, including PubMed, Web of Science and SPORTDiscus, was performed. On the basis of the search and inclusion criteria, four and six studies evaluating the effects of plant-based diets on aerobic and strength/power performances in humans were, respectively, included in the systematic review and meta-analysis. Plant-based diets had a moderate but positive effect on aerobic performance (0·55; 95 % CI 0·29, 0·81) and no effect on strength/power performance (-0·30; 95 % CI -0·67, 0·07). The altogether analyses of both aerobic and strength/power exercises revealed that athletic performance was unchanged (0·01; 95 % CI -0·21, 0·22) in athletes who adopted plant-based diets. However, a small negative effect on BMI (-0·27; 95 % CI -0·40, -0·15) was induced by these diets. The results indicate that plant-based diets have the potential to exclusively assist aerobic performance. On the other hand, these diets do not jeopardise strength/power performance. Overall, the predicted effects of plant-based diets on physical performance are impactless, even though the BMI of their adherents is reduced.

Use of ergogenic aids among Brazilian athletes: a cross-sectional study exploring competitive level, sex and sports.

Was investigated ergogenic aids (EAs) used by Brazilian athletes and their association with performance, sex, sports classification, and modality. It identified the main purposes of EAs and their prescription. Methods: 239 athletes of 15 modalities, ranging from regional to international level, answered a survey online. Results: Highly competitive athletes consumed nutritional and mechanical aids more (OR = 1.96 CI 95% [1.28-2.9]; OR = 1.79 CI 95% [1.29-2.47]), while the use of psychological EAs decreased [OR = 1.66 95% CI (1.18-2.94); p = 0.001]. Male athletes [OR = 1.44 CI 95% (1.11-2.88)] and individual sports practitioners [OR = 1.78 CI 95% (1.02-3.11)] used nutritional aids more. Triathlon athletes had higher nutritional EA use, while soccer athletes had lower. Combat sports athletes had higher pharmacological EA use. Conclusion: Athletes use nutritional and pharmacological aids more to improve performance and gain lean body mass. Mechanical aids were used for recovery and psychological aids for motivation. Self-prescription is common, especially for pharmacological aids.

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.

A Novel Wistar Rat Model of Obesity-Related Nonalcoholic Fatty Liver Disease Induced by Sucrose-Rich Diet.

The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is not fully understood, and experimental models are an alternative to study this issue. We investigated the effects of a simple carbohydrate-rich diet on the development of obesity-related NAFLD and the impact of physical training on the metabolic abnormalities associated with this disorder. Sixty Wistar rats were randomly separated into experimental and control groups, which were fed with sucrose-enriched (18% simple carbohydrates) and standard diet, respectively. At the end of each experimental period (5, 10, 20, and 30 weeks), 6 animals from each group were sacrificed for blood tests and liver histology and immunohistochemistry. From weeks 25 to 30, 6 animals from each group underwent physical training. The experimental group animals developed obesity and NAFLD, characterized histopathologically by steatosis and hepatocellular ballooning, clinically by increased thoracic circumference and body mass index associated with hyperleptinemia, and metabolically by hyperglycemia, hyperinsulinemia, hypertriglyceridemia, increased levels of very low-density lipoprotein- (VLDL-) cholesterol, depletion of the antioxidants liver enzymes superoxide dismutase and catalase, and increased hepatic levels of malondialdehyde, an oxidative stress marker. Rats that underwent physical training showed increased high-density lipoprotein- (HDL-) cholesterol levels. In conclusion, a sucrose-rich diet induced obesity, insulin resistance, oxidative stress, and NAFLD in rats.

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.

Temperature Control of Hypertensive Rats during Moderate Exercise in Warm Environment.

The control of body temperature in Spontaneously Hypertensive Rat (SHR) subjected to exercise in warm environment was investigated. Male SHR and Wistar rats were submitted to moderate exercise in temperate (25°C) and warm (32°C) environments while body and tail skin temperatures, as well as oxygen consumption, were registered. Total time of exercise, workload performed, mechanical efficiency and heat storage were determined. SHR had increased heat production and body temperature at the end of exercise, reduced mechanical efficiency and increased heat storage (p < 0.05). Furthermore, these rats also showed a more intense and faster increase in body temperature during moderate exercise in the warm environment (p < 0.05). The lower mechanical efficiency seen in SHR was closely correlated with their higher body temperature at the point of fatigue in warm environment (p < 0.05). Our results indicate that SHR exhibit significant differences in body temperature control during moderate exercise in warm environment characterized by increased heat production and heat storage during moderate exercise in warm environment. The combination of these responses result in aggravated hyperthermia linked with lower mechanical efficiency. Key PointsThe practice of physical exercise in warm environment has gained importance in recent decades mainly because of the progressive increases in environmental temperature;To the best of our knowledge, these is the first study to analyze body temperature control of SHR during moderate exercise in warm environment;SHR showed increased heat production and heat storage that resulted in higher body temperature at the end of exercise;SHR showed reduced mechanical efficiency;These results demonstrate that when exercising in a warm environment the hypertensive rat exhibit differences in temperature control.

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.

Construction and validation of lentiviral vector carrying rat neuronal nitric oxide synthase in vitro and in vivo.

In the present study, we developed a lentiviral vector with human cytomegalovirus promoter permitting high-level of nNOS expression. Neuronal cell line NG108 was used as an in vitro model to check the validity of gene transfer. The cells were infected with lenti-EGFP or lenti-nNOS particles for 24h. Lenti-nNOS infection in the NG108 cells induced dose dependent increase in mRNA and protein for nNOS; with a dose of 2.5 × 104 pfu/ml, nNOS mRNA expression increased by 40-fold while protein expression was increased by 2.5-fold compared to lenti-EGFP. Moreover, lenti-nNOS infection caused a greater increase in nNOS immunoreactivity in NG108 cells compared to lenti-EGFP as shown by immonocytochemistry. nNOS expression showed time dependent increases with lenti-nNOS infection with maximum up-regulation observed after two weeks of infection. Moreover, in vivo, unilateral injection of lenti-nNOS into the paraventricular nucleus (PVN) of rats induced a 27-fold increase of nNOS protein level in the injected side compared to non-injected side and this escalation was sustained up to three weeks. Overall, lenti-EGFP injection in the PVN did not show any significant change in nNOS expression. Furthermore, NADPH-diaphorase staining of nNOS in the PVN infected with lenti-nNOS induced a visible increase in nNOS expression compared with contralateral non-injected side up to three weeks. These results indicate that this approach of lentiviral mediated gene transfer of nNOS may provide a new means to up-regulate the nNOS expression for longer periods of time compared to adenoviral transfection and can be used as a research tool and potentially a therapy for chronic diseases involving impaired nNOS expression.

Contribution of the paraventricular nucleus in autonomic adjustments to heat stress.

We assessed the contribution of the paraventricular nucleus (PVN) in the heat stress-mediated changes in sympathetic nerve activity and blood flow redistribution from the core to the skin surface. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), heart rate (HR), and body and tail temperatures were recorded in anesthetized rats after bilateral microinjection of cerebrospinal fluid (CSF), lidocaine or NG-monomethyl-L-arginine (L-NMMA) into the PVN during heat stress. Heat stress was induced by a graded increase in the temperature of a heating pad for 30 min. Heat stimulus after blockade of the PVN with lidocaine resulted in a blunted RSNA response (ΔRSNA: 117.6 ± 17.0% versus 11.3 ± 7.3%), as well as blunted MAP and HR (ΔMAP: 22 ± 2 versus -0.04 ± 7.2 mmHg; ΔHR: 93.4 ± 9.3 versus 43.4 ± 18.8 bpm). Body temperature threshold for tail vasodilation was unaffected by lidocaine treatment. The increase in RSNA, MAP and HR due to heat stress in L-NMMA-treated rats reached similar levels as CSF-treated control rats. However, a higher body temperature threshold for tail vasodilation was observed after L-NMMA injection (37.3 ± 0.1 versus 37.8 ± 0.2 °C). In conclusion, an intact PVN contributes to an increase in renal sympathetic activity provoked by heat stress, resulting in cardiovascular adjustments that influence core blood redistribution to the periphery. Furthermore, during heat stress, the effect of the PVN on cutaneous vasodilation is dependent on a nitric oxide mechanism.

Effects of blockade of central dopamine D1 and D2 receptors on thermoregulation, metabolic rate and running performance.

To assess the effects of a blockade of central D1- and D2-dopaminergic receptors on metabolic rate, heat balance and running performance, 10 nmol (2 microl) of a solution of the D(1) antagonist SCH-23390 hydrochloride (SCH, n = 6), D2 antagonist eticlopride hydrochloride (Eti, n = 6), or 2 microl of 0.15 M NaCl (SAL, n = 6) was injected intracerebroventricularly into Wistar rats before the animals began graded running until fatigue (starting at 10 m/min, increasing by 1 m/min increment every 3 min until fatigue, 5% inclination). Oxygen consumption and body temperature were recorded at rest, during exercise and following 30 min of recovery. Control experiments with injection of two doses (10 and 20 nmol/rat) of either SCH or Eti solution were carried out in resting rats as well. Body heating rate, heat storage, workload and mechanical efficiency were calculated. Although SCH and Eti treatments did not induce thermal effects in resting animals, they markedly reduced running performance (-83%, SCH; -59% Eti, p < 0.05) and decreased maximal oxygen uptake (-79%, SCH; -45%, Eti, p < 0.05) in running rats. In addition, these treatments induced a higher body heating rate and persistent hyperthermia during the recovery period. Our data demonstrate that the alteration in dopamine transmission induced by the central blockade of dopamine- D1 and D2 receptors impairs running performance by decreasing the tolerance to heat storage. This blockade also impairs the dissipation of exercise-induced heat and metabolic rate recovery during the post-exercise period. Our results provide evidence that central activation of either dopamine- D1 or D2 receptors is essential for heat balance and exercise performance.

Central fatigue induced by losartan involves brain serotonin and dopamine content.

PURPOSE: To investigate the influence of angiotensin II (Ang II) AT1 receptors blockade on central fatigue induced by brain content of serotonin (5-HT) and dopamine (DA) during exercise. METHODS: Losartan (Los) was intracerebroventricularly injected in rats before running until fatigue (n = 6 per group). At fatigue, brains were quickly removed for measurement of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), DA, and 3,4-dihydroxyphenylacetic acid by high-pressure liquid chromatography in the preoptic area, hypothalamus, hippocampus, and frontal cortex. RESULTS: Intracerebroventricular injection of Los increased 5-HT content in the preoptic area and hypothalamus. Such results correlated positively with body heating rate and inversely with time to fatigue. On the other hand, time to fatigue was directly correlated with the diminished concentration of 5-HT in the hippocampus of Los rats. Although the levels of DA were not affected by Los treatment during exercise in any of the brain areas studied, a higher 5-HT/DA ratio was seen in the hypothalamus of Los animals. This higher hypothalamic 5-HT/DA ratio correlated positively with body heating rate and negatively with time to fatigue. CONCLUSIONS: Our results show that central fatigue due to hyperthermia and increased body heating rate induced by central Ang II AT1 receptor blockade in exercising rats is related with higher 5-HT content in the preoptic area and hypothalamus as well as with decreased levels of this neurotransmitter in the hippocampus. Furthermore, the interaction between 5-HT and DA within the hypothalamus seems to contribute to hyperthermia and premature central fatigue after angiotensinergic inhibition.

Central angiotensin AT1 receptors are involved in metabolic adjustments in response to graded exercise in rats.

To investigate the influence of central angiotensin AT1-receptors blockade on metabolic adjustments during graded exercise, Losartan (Los) was intracerebroventricularly injected in rats before running until fatigue. Oxygen consumption (VO2) was measured (n=6) and blood samples collected (n=7) to determine variations of glucose, lactate and free fatty acids (FFA). Los-rats exhibited a hyperglycemic response, already observed at 20% of maximal work, followed by a higher lactate levels and FFA mobilization from adipose tissue. Despite the reduced total time to fatigue and the higher VO2 associated with reduced mechanical efficiency, exercise led to the attainment of similar levels of effort in both groups. In summary, central AT1-receptor blockade during graded exercise induces hyperglycemia and higher FFA mobilization from adipose tissue at low exercise intensities in rats running at the same absolute exercise intensity. These data suggest that the central angiotensinergic system is involved in metabolic adjustments during exercise since central blockade of AT1-receptors shifts energy balance during graded exercise, similarly to situations of higher and premature sympathetic activation.

Performance-enhancing and thermoregulatory effects of intracerebroventricular dopamine in running rats.

To assess the role of central dopamine on metabolic rate, heat balance and running performance, 2.0 microL of 5 x 10(-3)M dopamine solution (DA) or 0.15M NaCl (SAL) was intracerebroventricularly injected in Wistar rats 1 min before running on a motor-driven treadmill, according to a graded exercise protocol, until fatigue. Oxygen consumption (VO(2)) and body temperature (T(b)) were recorded at rest, during exercise, and after 30 min of recovery. DA induced a marked increase in workload (approximately 45%, p<0.05). At fatigue point, DA-injected rats attained approximately 29% higher maximum oxygen consumption (VO(2max)) and approximately 0.75 degrees C higher T(b) than SAL-injected rats. Despite the higher VO(2max) and T(b) attained during exercise, DA-treated rats reached VO(2) basal values within the same recovery period and dissipated heat approximately 33% faster than SAL-treated rats (p<0.05). The mechanical efficiency loss rate was approximately 40% lower in DA than in SAL-treated rats (p<0.05), however, the heat storage was approximately 35% higher in the DA group (p<0.05). Our results demonstrate that increased DA availability in the brain has a performance-enhancing effect, which is mediated by improvements in the tolerance to heat storage and increases in the metabolic rate induced by graded exercise. These data provide further evidence that central activation of dopaminergic pathways plays an important role in exercise performance.

Central AT(1) receptor blockade increases metabolic cost during exercise reducing mechanical efficiency and running performance in rats.

The effect of central angiotensin AT(1) receptor blockade on metabolic rate and running performance in rats during exercise on a treadmill (18 m x min(-1), 5% inclination) was investigated. Oxygen consumption (VO(2)) was measured, using the indirect calorimetry system, while the animals were exercising until fatigue after injection of 2 microL of losartan (Los; 60 nmol, n=9), an angiotensin II AT(1) receptor antagonist, or 2 microL of 0.15 M NaCl (Sal, n=9) into the right lateral cerebral ventricle. Mechanical efficiency (ME) and workload (W) were calculated. The W performance by Los-treated animals was 29% lesser than in Sal-treated animals (p<0.02). During the first 10 min of exercise (dynamic state of exercise), there was a similar increase in VO(2), while ME remained the same in both groups. Thereafter (steady state of exercise), VO(2) remained stable in the Sal group but continued to increase and stabilized at a higher level in Los-treated animals until fatigue. During the steady state of exercise there was a sharper reduction in ME in Los-treated rats compared to Sal-treated animals (p<0.01) that was closely correlated to W (r=0.74; p<0.01). Our data showed that AT(1) receptor blockade increases metabolic cost during exercise, reducing mechanical efficiency. These results indicate that central angiotensinergic transmission modulates heat production, improving ME during the steady state of exercise.

Central nitric oxide inhibition modifies metabolic adjustments induced by exercise in rats.

The influence of the central nervous system on metabolic function is of interest in situations deviating from basal states, such as during exercise. Our previous study in rats demonstrated that central nitric oxide (NO) blockade increases metabolic rate, reducing mechanical efficiency during exercise. To assess the role of brain nitric oxide in the plasma glucose, lactate and free fatty acids (FFAs) concentrations of rats submitted to an incremental exercise protocol on a treadmill until fatigue, 1.43 micromol (2 microl) of N(omega)-nitro-l-arginine methyl ester (L-NAME, n=6), a NO synthase inhibitor, or 2 microl of 0.15M NaCl (SAL, n=6) was injected into the lateral cerebral ventricle (icv) of male Wistar rats immediately before exercise (starting at 10 m/min, with increments of 1m/min every 3 min until fatigue, 10% inclination). Blood samples were collected through a chronic jugular catheter at rest and during exercise until fatigue. During exercise, the L-NAME-treated animals had the following metabolic response compared to controls: (1) an increased hyperglycemic response during the first 60% of time to fatigue; (2) higher plasma lactate levels; and (3) a significant transitory increase in plasma free fatty acids during the dynamic phase of exercise that returned to basal levels earlier than controls during the steady state phase of exercise. In addition L-NAME-treated rats fatigued earlier than controls. The data indicate that the inhibition of the brain nitrergic system induced by icv L-NAME treatment disrupted the accuracy of the neural mechanism that regulates plasma glucose and free fatty acids mobilization during exercise in rats.

Central angiotensin AT1-receptor blockade affects thermoregulation and running performance in rats.

The effect of central angiotensin AT1-receptor blockade on thermoregulation in rats during exercise on a treadmill (18 m/min, 5% inclination) was investigated. Core (Tb) and skin tail temperatures were measured in rats while they were exercising until fatigue after injection of 2 microl of losartan (Los; 20 nmol, n = 4; 30 nmol, n = 4; 60 nmol, n = 7), an angiotensin II AT1-receptor antagonist, or 2 microl of 0.15 mol/l NaCl (Sal; n = 15) into the right lateral cerebral ventricle. Body heat rate (BHR), heat storage rate, threshold Tb for tail vasodilation (TTbV), time to fatigue, and workload were calculated. During exercise, the BHR and heat storage rate of Los-treated animals were, respectively, 40 and 53% higher (P < 0.01) than in Sal-treated animals. Additionally, rats injected with Los showed an increased TTbV (38.59 +/- 0.19 degrees C for Los vs. 38.12 +/- 0.1 degrees C for Sal, P < 0.02), a higher Tb at fatigue point (39.07 +/- 0.14 degrees C Los vs. 38.66 +/- 0.07 degrees C Sal, P < 0.01), and a reduced running performance (27.29 +/- 4.48 min Los vs. 52.47 +/- 6.67 min Sal, P < 0.01), which was closely related to the increased BHR. Our data suggest that AT1-receptor blockade attenuates heat dissipation during exercise due to the higher TTbV, leading to a faster exercise-induced increase in Tb, thus decreasing running performance.