Role of hypoxia-induced anorexia and right ventricular hypertrophy on lactate transport and MCT expression in rat muscle

To dissect the independent effects of altitude-induced hypoxemia and anorexia on the capacity for cardiac lactate metabolism, we examined the effects of 21 days of chronic hypobaric hypoxia (CHH) and its associated decrease in food intake and right ventricle (RV) hypertrophy on the monocarboxylate transporter 1 and 4 (MCT) expression, the rate of lactate uptake into sareolemmal vesicles, and the activity of lactate dehydrogenase isoforms in rat muscles. In comparison with control rats (C), I mmol/L lactate transport measured on skeletal muscle sarcolemmal vesicles increased by 33% and 58% in hypoxic (CHH, barometric pressure = 495 hPa) and rats pair-fed an equivalent quantity of food to that consumed by hypoxic animals, respectively. The increased lactate transport was higher in PF than in CHH animals (P <.05). No associated change in the expression of MCTI protein was observed in skeletal muscles, whereas MCTI mRNA decreased in CHH rats, in comparison with C animals (42%, P <.05), partly related to caloric restriction (30%, P <.05). MCT4 mRNA and protein increased during acclimatization to hypoxia only in slow-oxidative muscles (68%, 72%, P <.05, respectively). The MCT4 protein content did not change in the plantaris muscle despite a decrease in transcript levels, related to hypoxia and caloric restriction. In both the left and right ventricles, the MCT I protein content was unaffected by ambient hypoxia or restricted food consumption. These results suggest that MCTI and MCT4 gene expression in fast-glycolytic muscles is mainly regulated by posttranscriptional mechanisms. Moreover, the results emphasize the role played by caloric restriction on the control of gene expression in response to chronic hypoxia and suggest that hypoxia-induced right ventricle hypertrophy failed to alter MCT proteins. (c) 2005 Elsevier Inc. All rights reserved.