Aerobic Swim Training Restores Aortic Endothelial Function by Decreasing Superoxide Levels in Spontaneously Hypertensive Rats.

OBJECTIVE:: We aimed to determine whether aerobic training decreases superoxide levels, increases nitric oxide levels, and improves endothelium-dependent vasodilation in the aortas of spontaneously hypertensive rats. METHODS:: Spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were distributed into 2 groups: sedentary (SHRsd and WKYsd, n=10 each) and swimming-trained (SHRtr, n=10 and WKYtr, n=10, respectively). The trained group participated in training sessions 5 days/week for 1 h/day with an additional work load of 4% of the animal's body weight. After a 10-week sedentary or aerobic training period, the rats were euthanized. The thoracic aortas were removed to evaluate the vasodilator response to acetylcholine (10-10 to 10-4 M) with or without preincubation with L-NG-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10-4 M) in vitro. The aortic tissue was also used to assess the levels of the endothelial nitric oxide synthase and nicotinamide adenine dinucleotide oxidase subunit isoforms 1 and 4 proteins, as well as the superoxide and nitrite contents. Blood pressure was measured using a computerized tail-cuff system. RESULTS:: Aerobic training significantly increased the acetylcholine-induced maximum vasodilation observed in the SHRtr group compared with the SHRsd group (85.9±4.3 vs. 71.6±5.2%). Additionally, in the SHRtr group, superoxide levels were significantly decreased, nitric oxide bioavailability was improved, and the levels of the nicotinamide adenine dinucleotide oxidase subunit isoform 4 protein were decreased compared to the SHRsd group. Moreover, after training, the blood pressure of the SHRtr group decreased compared to the SHRsd group. Exercise training had no effect on the blood pressure of the WKYtr group. CONCLUSIONS:: In SHR, aerobic swim training decreased vascular superoxide generation by nicotinamide adenine dinucleotide oxidase subunit isoform 4 and increased nitric oxide bioavailability, thereby improving endothelial function.

Aerobic Swim Training Restores Aortic Endothelial Function by Decreasing Superoxide Levels in Spontaneously Hypertensive Rats

OBJECTIVE: We aimed to determine whether aerobic training decreases superoxide levels, increases nitric oxide levels, and improves endothelium-dependent vasodilation in the aortas of spontaneously hypertensive rats. METHODS: Spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were distributed into 2 groups: sedentary (SHRsd and WKYsd, n=10 each) and swimming-trained (SHRtr, n=10 and WKYtr, n=10, respectively). The trained group participated in training sessions 5 days/week for 1 h/day with an additional work load of 4% of the animal’s body weight. After a 10-week sedentary or aerobic training period, the rats were euthanized. The thoracic aortas were removed to evaluate the vasodilator response to acetylcholine (10-10 to 10-4 M) with or without preincubation with L-NG-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10-4 M) in vitro. The aortic tissue was also used to assess the levels of the endothelial nitric oxide synthase and nicotinamide adenine dinucleotide oxidase subunit isoforms 1 and 4 proteins, as well as the superoxide and nitrite contents. Blood pressure was measured using a computerized tail-cuff system. RESULTS: Aerobic training significantly increased the acetylcholine-induced maximum vasodilation observed in the SHRtr group compared with the SHRsd group (85.9±4.3 vs. 71.6±5.2%). Additionally, in the SHRtr group, superoxide levels were significantly decreased, nitric oxide bioavailability was improved, and the levels of the nicotinamide adenine dinucleotide oxidase subunit isoform 4 protein were decreased compared to the SHRsd group. Moreover, after training, the blood pressure of the SHRtr group decreased compared to the SHRsd group. Exercise training had no effect on the blood pressure of the WKYtr group. CONCLUSIONS: In SHR, aerobic swim training decreased vascular superoxide generation by nicotinamide adenine dinucleotide oxidase subunit isoform 4 and increased nitric oxide bioavailability, thereby improving endothelial function.

The importance of animal studies in exercise science

Abstract The validity and relevance of research with animals for the development of knowledge in Exercise Science have for long been discussed. Given the complexity of the biological systems, the use of animal models offers a significant contribution to uncover new findings about acute and chronic effects of exercise, particularly when these studies in humans have limitations and ethical implications. There have been notable findings using experimental animals either in basic sciences or in clinical studies involving physiology, pharmacology, genetic, biochemistry, urology, endocrinology and cancer. This article presents a brief review of scientific research using animal models with a focus on exercise training as an effective tool for the prophylaxis and treatment of different pathological processes, which are the basis of many concepts taught and used in undergraduate courses and graduate programs, as well as in new researches showed in scientific conference meetings in numerous areas of science.(AU)

Loss of strength capacity is associated with mortality, but resistance exercise training promotes only modest effects during cachexia progression.

AIMS: Resistance exercise training (RET) has been adopted as non-pharmacological anti-catabolic strategy. However, the role of RET to counteract cancer cachexia is still speculative. This study aimed to verify whether short-term RET would counteract skeletal muscle wasting in a severe cancer cachexia rat model. MAIN METHODS: Wistar rats were randomly allocated into four experimental groups; 1) untrained control rats (control), 2) rats submitted to RET (control+RET), 3) untrained rats injected with Walker 256 tumor cells in the bone marrow (tumor) and 4) rats injected with Walker 256 tumor cells in the bone marrow and submitted to RET (tumor+RET). KEY FINDINGS: Tumor group displayed skeletal muscle atrophy fifteen days post tumor cells injection as assessed by plantaris (-20.5%) and EDL (-20.0%) muscle mass. EDL atrophy was confirmed showing 43.8% decline in the fiber cross sectional area. Even though RET increased the lactate dehydrogenase protein content and fully restored phosphorylated form of 4EBP-1 to the control levels in skeletal muscle, it failed to rescue muscle morphology in tumor-bearing rats. Indeed, RET did not mitigated loss of muscle function, anorexia, tumor growth or mortality rate. However, loss of strength capacity (assessed by 1-RM test performance) demonstrated a negative correlation with rats' survival (p=0.02; r=0.40), suggesting that loss of strength capacity might predict cancer mortality. SIGNIFICANCE: These results demonstrated that bone marrow injection of Walker 256 tumor cells in rats induces cancer cachexia, strength capacity is associated with cancer survival and short-term RET promotes only modest effects during cachexia progression.

Exercise improves endothelial function: a local analysis of production of nitric oxide and reactive oxygen species.

This study aimed at investigating the acute effects of aerobic exercise on endothelium-dependent vasomotor function of rat aorta, as well as mechanisms involved in endothelial nitric oxide (NO) bioactivity. Wistar rats were assigned to either a resting control (C, n = 21) or acutely exercised (E, n = 21) groups (60 min, 55-60% of maximum speed). After exercise, thoracic aorta was excised and cut into rings. Two rings were promptly applied to evaluate vasomotor function and the rest of aorta was used for additional measurements. Acute exercise significantly improved maximum ACh-induced relaxation (C, 91.6 ± 1.2 vs. E, 102.4 ± 1.7%, p < 0.001) and sensitivity to ACh (C, -7.3 ± 0.06 vs. E, -7.3 ± 0.02 log M, p < 0.01), and was accompanied by significantly increases on serine1177 eNOS phosphorylation, reflecting its enhanced activation. However, acute exercise also enhanced both superoxide and hydrogen peroxide production, as assayed by dihydroethidium oxidation, lucigenin chemiluminescence and Amplex Red assays. We also provided evidence for Nox2 NADPH oxidase (Nox) activation through gp91dstat-mediated inhibition of superoxide signals. Enhanced arterial relaxations associated with acute exercise were nearly-completely prevented by catalase, suggesting a role for paracrine hydrogen peroxide. Despite increased detectable oxidant generation, cellular oxidative stress was not evident, as suggested by unaltered GSH:GSSG ratio and lipid hydroperoxides. Collectively, these results demonstrate that one bout of moderate aerobic exercise improves endothelial function by increasing NO bioavailability, while superoxide and hydrogen peroxide are generated in a controlled fashion.

A single bout of moderate-intensity exercise increases vascular NO bioavailability and attenuates adrenergic receptor-dependent and -independent vasoconstrictor response in rat aorta.

The present study investigated the effect of one bout of moderate-intensity exercise on the adrenergic receptor-dependent and -independent vasoconstrictor response in rat aortas, and the role of nitric oxide (NO) bioavailability on these vasomotor responses. One group of rats was submitted to a 60 min of exercise at approximately 60% of maximal exercise capacity on a treadmill (exercise group) and the other one was placed in the treadmill without running (control group). Immediately after this period, both groups were euthanized and the thoracic aorta was removed to evaluate the vasoconstrictor response to norepinephrine and potassium chloride, and to evaluate the vascular nitrite and nitrate concentration. One bout of exercise attenuated the maximal contractile response to both norepinephrine and potassium chloride compared to control group. These differences on vascular reactivity were not observed in endothelium-denuded aortic rings and aortic rings pre-incubated with a nitric oxide synthesis inhibitor. Additionally, exercise group increased NO bioavailability (nitrite and nitrate concentration) as compared to control group. These results demonstrate that one bout of moderate-intensity exercise is able to attenuate adrenergic receptor-dependent and -independent vasoconstrictor response in rat aorta, mainly by increasing vascular NO bioavailability.

Moderate exercise training decreases aortic superoxide production in myocardial infarcted rats.

Myocardial infarction (MI) has been associated with increases in reactive oxygen species (ROS). Exercise training (ET) has been shown to exert positive modulations on vascular function and the purpose of the present study was to investigate the effect of moderate ET on the aortic superoxide production index, NAD(P)H oxidase activity, superoxide dismutase activity and vasomotor response in MI rats. Aerobic ET was performed during 11 weeks. Myocardial infarction significantly diminished maximal exercise capacity, and increased vasoconstrictory response to norepinephrine, which was related to the increased activity of NAD(P)H oxidase and basal superoxide production. On the other hand, ET normalized the superoxide production mostly due to decreased NAD(P)H oxidase activity, although a minor SOD effect may also be present. These adaptations were paralleled by normalization in the vasoconstrictory response to norepinephrine. Thus, diminished ROS production seems to be an important mechanism by which ET mediates its beneficial vascular effects in the MI condition.

Exercício físico e disfunção endotelial / Exercise and endothelial dysfunction

A disfunção endotelial apresenta papel de destaque no desenvolvimento e na progressão da aterosclerose por estar diretamente relacionada a alterações na homeostase da parede vascular e no controle da circulação. Estudos clínicos e experimentais têm evidenciado efeitos benéficos do treinamento físico...

Efeitos do treinamento físico aeróbio sobre a bioatividade do óxido nítrico e a vasodilatação aórtica / Effects of aerobic exercise training opon nitric oxide bioactivity and aorta vasodilatation

O treinamento físico aeróbio (TF) é um importante meio para melhorar a função endotelial. Entretanto, como os vasos se adaptam ao TF ainda não está completamente esclarecido. Desta forma, o presente estudo teve por objetivo investigar, em ratos normotensos, os efeitos do TF sobre a via de produção de óxido nítrico (NO) e a defesa antioxidante vascular, e suas conseqüências sobre a resposta vasodilatadora em aorta isolada. Os ratos foram submetidos a um protocolo de TF aeróbio (esteira rolante, ~55%Veloc. Máx; cinco sessões/sem., 60 min/sessão, período de 11 semanas). Após o TF, foi avaliada a função vasomotora “in vitro” pela curva de concentração-efeito à acetilcolina (ACh) e ao nitroprussiato de sódio (NPS), e realizadas medidas bioquímicas na aorta. O programa de TF aumentou significativamente (P < 0,05) em 62% a expressão da enzima óxido nítrico sintase endotelial (eNOS). Entretanto, o TF não modificou significativamente a expressão e atividade da enzima antioxidante superóxido dismutase.Além disso, o TF não modificou o relaxamento individual e a sensibilidade à ACh. Por outro lado, o TF diminuiu significativamente a sensibilidade ao NPS (-8,26 ± 0,081 vs. -7,79 ± 0,099 Log [M], S vs T, respectivamente, P < 0,001). Os resultados apresentados demonstram que o TF aeróbio foi capaz de alterar um dos mecanismos envolvidos na bioatividade do NO, marcadamente o aumento da expressãoda eNOS. Entretanto, esta modificação não levou à melhora da responsividade vasodilatadora aórtica estimulada pela acetilcolina e provocou menor sensibilidade ao NPS.

Aerobic training (AT) is an important way to improve endothelial function. However, it is not completelyunderstood how the blood vessels adapt themselves to the AT. Therefore, the aim of this study was to investigate exercise training-induced adaptations on the nitric oxide (NO) production, antioxidant defense and aorta vasodilatation in normotensive rats. The rats were subjected to an AT protocol (treadmill,~55% Max Veloc., 5 bouts/week, 60 min/bout, 11 wks). After the AT, it was examined in vitro vasomotor function to acetylcholine (ACh) and sodium nitroprusside (SNP), and biochemical analysis in the aorta. Aerobic training significantly increased (P < 0.05) by 62% the expression of the endothelial nitric oxide synthase (eNOS). However, ET did not modify the relaxation response and sensitivity to ACh. In contrast, AT significantly reduced aortic sensitivity to SNP (-8.26 ± 0.081 vs. -7.79 ± 0.099 Log [M], Sed vs. AT,respectively, P < 0.001). These results demonstrate that aerobic AT was able to modify one important mechanism related to the NO bioactivity, which is the increase of eNOS expression. However, this response did not contribute to improve of the aortic vasodilatation response to acetylcholine and decreased the sensitivity to SNP.