In the striatum of the rat the enzyme nitric oxide synthase (NOS) is present in a dense fiber network and in relatively few medium sized, none spinal neurons. This NOS is activated by glutamate to synthesize nitric oxide(NO). A sustained, strong activation of NOS caused by excessive release of glutamate, results in strongly increased NO levels in this tissue. NO can combine with oxygen radical species to yield the toxic compound peroxynitrite(ONOO-). In severe perinatal asphyxia (SPA), -performed immersing during >20 min in water bath at 37°C uterus-containing fetus at term obtained by histerectomy- this mechanism may underlie the oxidative stress afflicted by this model. Oxidative stress may induce NOS-II in neuronal and/or glial cells, and, in addition, also heme oxygenase -1.
Therefore we chose to study cGMP levels in the striatum as an indicator for increased production of either NO or CO. The localization of NOS-II and heme oxygenase-1 were studied by immunocytochemistry. cGMP levels were assayed in the presence of 1 mM IBMX, in in vitro incubated striatal slices, using a normal RIA procedure. cGMP levels in striatal tissue from control pups(PN10) were 5.2 pmol/mg protein and in the SPA group cGMP levels were 9.4 pmol/mg protein which is an increase of ≈40% (p<0.01 compared to controls). L-NAME at 0.1 mM decreased cGMP levels in control pups and SPA pups, although cGMP levels in the SPA group were still increased compared to the control group. Nitroprusside stimulated cGMP showed not differences between both groups.
