HYPOTHERMIA DURING OR AFTER SEVERE PERINATAL ASPHYXIA PREVENTS INCREASE IN CYCLIC GMP-RELATED NITRIC-OXIDE LEVELS IN THE NEWBORN RAT STRIATUM

The striatum is rich in nitric oxide synthase (NOS). It is present in a dense fiber network and in a few medium-sized non-spiny interneurons . Previous work showed chronic overexpression of NOS in the rat striat um after a severe perinatal asphyctic (SPA) insult. This was prevented by hypothermia. We investigated whether the overexpression of NOS was accompanied by increased NOS activity. As nitric oxide (NO) is a pote nt activator of the soluble isoform of guanylyl cyclase, we measured s triatal 3',5'-cyclic monophosphate (cyclic GMP) synthesis in 10-day-ol d (P10) rat pups that were subjected to SPA during normothermia or hyp othermia during or after the insult. Cyclic GMP levels in striatal tis sue from control pups were similar to 25.8 pmol/mg protein and in the SPA group similar to 38.1 pmol/mg protein (p < 0.01). Hypothermia, dur ing as well as after insult, prevented this increase of cyclic GMP. N- omega-nitro-L-arginine (L-NAME) (0.1 mM) decreased cyclic GMP levels i n control, SPA and hypothermia treated pups to similar low levels (sim ilar to 8% of level without L-NAME). Sodium nitroprusside (SNP) stimul ated cyclic GMP showed no differences between the four groups. This in dicates that high cyclic GMP levels in the striatum of rats subjected to SPA are caused by increased NOS activity. Hypothermia after an asph yctic insult could be a promising treatment. (C) 1998 Elsevier Science B.V.