CYTOSOLIC AND MEMBRANE-BOUND CEREBRAL NITRIC-OXIDE SYNTHASE ACTIVITY DURING HYPOXIA IN CORTICAL TISSUE OF NEWBORN PIGLETS

To determine the role of nitric oxide production during hypoxia, the p resence of two forms of neuronal nitric oxide synthase, cytosolic (cNO S) and membrane-bound (memNOS), in cortical tissue of newborn piglets and the effects of hypoxia on the activity of these enzymes were studi ed. Experiments were performed in 12 anesthetized and ventilated Yorks hire piglets, 2-4 days of age. Hypoxia was induced by decreasing the F iO(2) to 0.07. The control group was ventilated maintaining normoxia. After 1 h of normoxic or hypoxic ventilation brain tissue was removed and frozen immediately in liquid nitrogen. Tissue hypoxia was confirme d by analysis of adenosine triphosphate (ATP) and phosphocreatine (PCr ): ATP was reduced to 52% and PCr to 28% of control values, cNOS activ ity was 35.3 +/- 13.7 pmol/mg protein per min in the control group and 28.3 +/- 7.0 in the hypoxia group; memNOS activity was 10.5 +/- 4.5 a nd 12.0 +/- 3.9 pmol/mg protein per min in the control and hypoxia gro ups, respectively. Differences in cNOS and memNOS activity between con trol and hypoxic animals were not significant. The results indicate th at both cNOS and memNOS are present in cortical tissue of newborn pigl ets and that the activity is unaffected by 1 h of tissue hypoxia. We s uggest that production of nitric oxide and its derivative peroxynitrit e during hypoxia may therefore be a potential mechanism for hypoxia-in duced brain cell membrane lipid peroxidation.