RESUMO
AIM: Involvement of oxidative stress and nitric oxide synthase (NOS) isoforms in skeletal muscle cellular adaptations to chronic heart failure (CHF) is controversial, and possible muscle fibre-type heterogeneity in the oxidative stress and NOS responses to CHF have not been examined. Consequently, we hypothesized that the changes in determinants of elevated oxidative and nitrosylative stress associated with CHF would occur in skeletal muscle and would be similar in predominantly type I slow twitch muscle (soleus) and type II fast twitch muscle (plantaris) of rats. METHODS: The purpose of this study was to measure NOS isoforms (endothelial, inducible and neuronal NOS) and antioxidant enzymes (SOD-1, SOD-2, catalase) by protein immunoblot as well as markers of oxidative stress by biochemical assays in soleus and plantaris muscle sections of the rat hind limb. This was performed for control and post-infarction, compensated CHF rats. RESULTS: Twelve weeks after coronary artery ligation-induced moderate CHF, soleus exhibited decreased SOD-1, SOD-2 and eNOS, but increased iNOS and nNOS isoforms assessed by immunoblot. This was associated with elevated lipid and DNA oxidative damage assessed by biochemical assays. In contrast, plantaris muscle exhibited no changes in antioxidant enzymes or NOS isoforms, and had lower lipid and DNA oxidative damage. CONCLUSION: These observations suggest a heretofore unreported muscle fibre-type-specific response of oxidative stress and NOS isoforms to CHF is of importance in understanding the cellular mechanisms of skeletal muscle dysfunction in CHF.
Assuntos
Adaptação Fisiológica , Insuficiência Cardíaca/metabolismo , Fibras Musculares Esqueléticas/enzimologia , Músculo Esquelético/enzimologia , Óxido Nítrico Sintase/análise , Estresse Oxidativo , Animais , Dano ao DNA , Glutationa/sangue , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Immunoblotting , Peroxidação de Lipídeos , Masculino , Fibras Musculares de Contração Rápida/enzimologia , Fibras Musculares de Contração Rápida/patologia , Fibras Musculares Esqueléticas/patologia , Fibras Musculares de Contração Lenta/enzimologia , Fibras Musculares de Contração Lenta/patologia , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Peptidil Dipeptidase A/análise , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
We examined the effects of 8 wk of intense endurance training on free fatty acid (FFA) transporters and metabolism in resting and contracting soleus muscle using pulse-chase procedures. Endurance training increased maximal citrate synthase activity in red muscles (+54 to +91%; P = 0.05) but failed to increase cytosolic fatty acid binding protein content, mRNA for fatty acyl-CoA synthase, and the putative FFA transporters or transport of palmitic acid into giant sarcolemmal vesicles. At rest, only triacylglycerol (TG) synthesis was significantly increased by training (+100.9 +/- 8.7 vs. +66.6 +/- 6.7 nmol/g wet wt; P = 0.05). Muscle contraction increased TG synthesis (+46%; P = 0.05) and palmitate oxidation (+115%; P = 0.05) in untrained rats. Endurance training further enhanced synthesis of monoacylglycerol (MG), diacylglycerol (DG) and TG during contraction (+36, +69 and +71%, respectively; P = 0.05), as well as exogenous palmitate oxidation (+41%; P = 0.05) relative to untrained rats. Compared with those in untrained rats, TG breakdown and oxidation during contraction were reduced after training by 49 and 30%, respectively (P = 0.05). In conclusion, endurance training 1) increases FFA oxidation and incorporation into endogenous lipid pools during contraction and 2) reduces the rate of intramuscular TG utilization during contraction when exogenous FFA availability is adequate. The enhanced FFA uptake subsequent to training appears to be independent of altered maximal transport rates of FFA into the muscle cell.