ACTIVATION OF NITRIC-OXIDE SYNTHASE GENE-EXPRESSION BY HYPOXIA IN CENTRAL AND PERIPHERAL NEURONS

In the present study we examined the effects of hypobaric hypoxia on n euronal (n) and endothelial (e) nitric oxide synthase (NOS) gene expre ssion in the central and peripheral nervous system. Adult rats were ex posed either to normoxia (room air) or to hypobaric hypoxia (0.4 atm) for 4, 12 or 24 h and cerebellum and nodose ganglion representing the central and peripheral neurons, respectively, were removed. Messenger RNAs encoding n- and eNOS as well as beta-actin were analyzed by rever se transcriptase polymerase chain reaction (RT-PCR) technique. Hypoxia increased nNOS mRNA expression with maximal changes occurring after 1 2 h wherein mRNA levels were increased by 10.4 +/- 1.3 and 2 +/- 0.4 f old in nodose ganglion and cerebellum, respectively. Hypoxia, on the o ther hand, had no significant effect on eNOS and beta-actin mRNA level s. Analysis of nNOS protein and enzyme activity showed near doubling o f these variables in both tissues after 24 h of hypoxia, indicating th at nNOS protein levels are increased and that the protein is functiona lly active. These observations demonstrate that 12-24 h of hypobaric h ypoxia selectively activates nNOS gene expression, which is reflected in an increase in nNOS protein in central and peripheral neurons. It i s suggested that up-regulation of nNOS leads to increased generation o f nitric oxide, which in turn may contribute to the readjustments of c ardio-respiratory systems during the early stages of chronic hypoxia.