CONICET | Buscador de Institutos y Recursos Humanos

Studies in our laboratory showed that exposure of rats to hypobaric hypoxia increased the tolerance of heart to hypoxia/reoxygenation (H/R), involving mitochondrial and cytosolic NOS systems. The objective of the present study was to evaluate how the degree of somatic maturation could alter this healthy response.Prepubertal male rats were exposed 48 h to 4400 m simulated altitude in a hypobaric chamber (HH). The mechanic-energetic activity in perfused hearts and the contractile functional capacity of nitric oxide synthase (NOS) in isolated left ventricle papillary muscles (PM) were evaluated during H/R. Cytosolic nitric oxide (NO), nitrites/nitrates (Nx-) production, NOS isoforms expression, mitochondrial O2 consumption and ATP production were also evaluated.Heart left ventricular pressure (LVP) during H/R was not improved by HH. However the energetic activity (Ht) was increased. Thus, the contractile economy (LVP/Ht) got worse in HH. Nitric oxide did not modify PM contractility after H/R. Cytosolic p-eNOS and iNOS expression were decreased by HH but no changes were observed in NO production. Interestingly, HH increased Nx levels but O2 consumption and ATP production in mitochondria were not affected by HH. Conclusions: prepubertal rats exposed to HH preserved cardiac contractile function, but with a high energetic cost, modifying contractile economy. Although this could be related to the decreased NOS expression detected, cytosolic NO production was preserved, may be through the Nx metabolic pathway, without modifying mitochondrial ATP production and O2 consumption. In that scenario, the treatment was unable to increase tolerance to H/R as we observed in adult animals.