Regulation of diaphragmatic nitric oxide synthase expression during hypobaric hypoxia

Nitric oxide (NO) is normally synthesized inside skeletal muscle fibers by both endothelial (eNOS) and neuronal (nNOS) nitric oxide synthases. In this study, we evaluated the influence of hypobaric hypoxia on the expression o f NOS isoforms, argininosuccinate synthetase (AS), argininosuccinate lyase (AL), and manganese superoxide dismutase (Mn SOD) in the ventilatory muscle s. Rats were exposed to hypobaric hypoxia (similar to 95 mmHg) from birth f or 60 days or 9-11 mo. Age-matched control groups of rats also were examine d. Sixty days of hypoxia elicited approximately two-and ninefold increases in diaphragmatic eNOS and nNOS protein expression (evaluated by immunoblott ing), respectively, and about a 50% rise in diaphragmatic NOS activity. In contrast, NOS activity and the expression of these proteins declined signif icantly in response to 9 mo of hypoxia. Hypoxia elicited no significant alt erations in AS, AL and Mn SOD protein expression. Moreover, the inducible N OS (iNOS) was not detected in normoxic and hypoxic diaphragmatic samples. W e conclude that diaphragmatic NOS expression and activity undergo significa nt adaptations to hypobaric hypoxia and that iNOS does not participate in t his response.