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Effects of sildenafil on the gastrocnemius and cardiac muscles of rats in a model of prolonged moderate exercise training.

ABSTRACT: Moderate exercise training improves energetic metabolism, tissue perfusion and induces cardiac and skeletal muscle remodeling. Sildenafil, a potent phosphodiesterase-5 inhibitor used to treat erectile dysfunction, reduces infarct size and increases tissue oxygenation in experimental models of cardiovascular disease. We have evaluated the effects of prolonged moderate exercise training and a repeat administration of sildenafil on the rat gastrocnemius and cardiac muscles. Animals were divided into two groups: sedentary and trained. Each group was subdivided into animals treated with vehicle or with two doses of sildenafil (10 or 15 mg/kg/day) during the last week of training. Physical exercise did not induce cardiac hypertrophy, whereas it increased mRNA levels of the PGC-1?, HIF-1? and VEGF genes, which are involved in mitochondrial biogenesis and angiogenesis, and reduced mRNA levels of FoxO3a, MuRF-1 and Atrogin-1. Sildenafil dose-dependently promoted both angiogenesis, as shown by increased capillary density, and muscle atrophy, as shown by muscle fibre size. These effects were more pronounced in trained animals. Our data confirm the beneficial effects of a moderate and prolonged training on cardiovascular and skeletal systems and document the positive and negative effects of sildenafil on these tissues at doses higher than those used in clinical practice. This report may impact on the use of sildenafil as a substance able to influence sports performance.

SUBMITTER: Rinaldi B

PROVIDER: S-EPMC3726744 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Effects of sildenafil on the gastrocnemius and cardiac muscles of rats in a model of prolonged moderate exercise training.

Rinaldi Barbara B Donniacuo Maria M Sodano Loredana L Gritti Giulia G Signoriello Simona S Parretta Elisabetta E Berrino Liberato L Urbanek Konrad K Capuano Annalisa A Rossi Francesco F

PloS one 20130729 7

Moderate exercise training improves energetic metabolism, tissue perfusion and induces cardiac and skeletal muscle remodeling. Sildenafil, a potent phosphodiesterase-5 inhibitor used to treat erectile dysfunction, reduces infarct size and increases tissue oxygenation in experimental models of cardiovascular disease. We have evaluated the effects of prolonged moderate exercise training and a repeat administration of sildenafil on the rat gastrocnemius and cardiac muscles. Animals were divided int ...[more]

PMID: 23922868

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Project description:Aging is associated with testicular morphological and functional alterations, but the underlying molecular mechanisms and the impact of physical exercise are poorly understood. In this study, we examined the effects of age and lifelong moderate-intensity exercise on rat testis. Mature adults (35 weeks) and middle-aged (61 weeks) Wistar Unilever male rats were maintained as sedentary or subjected to a lifelong moderate-intensity treadmill training protocol. Testis weight and histology, mitochondrial biogenesis and function, and proteins involved in protein synthesis and stress response were evaluated. Our results illustrate an age-induced testicular atrophy that was associated with alterations in stress response, and mitochondrial biogenesis and function. Aging was associated with increased testicular levels of heat shock protein beta-1 (HSP27) and antioxidant enzymes. Aging was also associated with decreased mRNA abundance of the nuclear respiratory factor 1 (Nrf1), a key transcription factor for mitochondrial biogenesis, which was accompanied by decreased protein levels of the oxidative phosphorylation system (OXPHOS) complexes subunits in the testes of older animals. On the other hand, exercise did not protect against age-induced testicular atrophy and led to deleterious effects on sperm morphology. Exercise led to an even more pronounced decrease in the Nrf1 mRNA levels in testes of both age groups and was associated with decreased mRNA abundance of other mitochondrial biogenesis markers and decreased protein levels of OXPHOS complexes subunits. Lifelong moderate-intensity exercise training was also associated with an increase in testicular oxidative stress markers and possibly with reduced translation. Together, our results indicate that exercise did not protect against age-induced testicular atrophy and was not associated with beneficial changes in mitochondria and stress response, further activating mechanisms of protein synthesis inhibition.

Project description:Background:Metabolic Syndrom has become a public health problem. It mainly results from the increased consumption of fat and sugar. In this context, the benefits of personalized moderate exercise training were investigated on a metabolic syndrome male wistar rat model food with fructose drinking water (20-25% w/v). Different markers including body weight, metabolic measurements, blood biochemistry related to metabolic syndrome complications have been evaluated. Methods:Male Wistar rats were randomly allocated to 4 groups: control (sedentary (C, n?=?8) and exercise trained (Ex, n?=?8)), fructose fed (sedentary (FF, n?=?8) and exercise trained fructose fed rats (ExFF, n?=?10)). ExFF and Ex rats were trained at moderate intensity during the last 6 weeks of the 12 weeks-long protocol of fructose enriched water. Metabolic control was determined by measuring body weight, fasting blood glucose, HOMA 2-IR, HIRI, MISI, leptin, adiponectin, triglyceridemia and hepatic dysfunction. Results:After 12 weeks of fructose enriched diet, rats displayed on elevated fasting glycaemia and insulin resistance. A reduced food intake, as well as increased body weight, total calorie intake and heart weight were also observed in FF group. Concerning biochemical markers, theoretical creatinine clearance, TG levels and ASAT/ALAT ratio were also affected, without hepatic steatosis. Six weeks of 300 min/week of moderate exercise training have significantly improved overweight, fasting glycaemia, HOMA 2-IR, MISI without modify HIRI. Exercise also decreased the plasma levels of leptin, adiponectin and the ratio leptin/adiponectin. Regarding liver function and dyslipidemia, the results were less clear as the effects of exercise and fructose-enriched water interact together, and, sometimes counteract each other. Conclusion:Our results indicated that positive health effects were achieved through a personalized moderate training of 300 min per week (1 h/day and 5 days/week) for 6 weeks. Therefore, regular practice of aerobic physical exercise is an essential triggering factor to attenuate MetS disorders induced by excessive fructose consumption.

Project description:Genes can be activated or inhibited by signals within the tissues in response to an acute bout of exercise. It is unclear how a particular aerobic exercise bout may influence two muscles with similar actions to the activity. Therefore, the purposes of this investigation was to determine the gene response of selected genes involved in the "stress" response of the gastrocnemius (fast-twitch) and soleus (slow-twitch) muscles to a single two hour aerobic exercise bout in female Sprague-Dawley Rats at the 1 hour time point after the exercise. Exercised rats were run (n=8) for 2 hours at 20 m.min(-1) and one hour after the completion of the bout had their soleus (S) and gastrocnemius (G) muscles removed. Age and timed matched sedentary control rats had both S and G muscles removed also. RNA was isolated from all muscles. Real-time PCR analysis was performed on the following genes: NFκB, TNFα, and Atf3. GAPDH was used as the housekeeping gene for both muscles. S muscle showed more genes altered (n = 52) vs G (n = 26). NFκB gene expression was 0.83 ± 0.14 in the exercised S but was + 1.36 ± 0.58 in the exercised G and was not significantly different between the muscles. TNFα was altered 1.30 ± 0. 34 in the exercised S and 1.36 ± 0.71 in the exercised G and was not significantly different between the muscles. The gene Atf3 was significantly altered at 4.97 ± 1.01 in the exercised S, while it was not significantly altered in the exercised G (0.70 ± 0.55). This study demonstrates that an acute bout of aerobic exercise can alter gene expression to a different extent in both the S and G muscles. It is highly likely that muscle recruitment was a factor which influenced the gene expression in theses muscles. It is interesting to note that some genes were similarly activated in these two muscles but other genes may demonstrate a varied response to the same exercise bout depending on the type of muscle. Key pointsThe soleus (primarily slow twitch) and the gastrocnemius (primarily fast type) do not respond the same to a given exercise bout.There are gene transcription differences in stress genes between the 2 muscles.The results of exercise studies should be carefully viewed as the muscle used in measurements may not provide an adequate representation of all skeletal muscles.

Dataset Information

Effects of sildenafil on the gastrocnemius and cardiac muscles of rats in a model of prolonged moderate exercise training.

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Effects of sildenafil on the gastrocnemius and cardiac muscles of rats in a model of prolonged moderate exercise training.

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