Differential regulation of cyclic GMP levels in the frontal cortex and the cerebellum of anesthetized rats by nitric oxide: an in vivo microdialysis study

A microdialysis method combined with a sensitive radioimmunoassay was used to monitor extracellular cyclic GMP (cGMP) levels in the frontal cortex and the cerebellum of anesthetized rats in vivo. Basal cGMP release remained constant throughout the perfusion period and was ≈ 2 fmol/30 min in the frontal cortex and ≈ 4 fmol/30 min in the cerebellum. The nitric oxide (NO) donor sodium nitroprusside (SNP) stimulated cGMP release transiently in both regions. However, the maximal response was 3-fold in the frontal cortex (obtained with 5 μM SNP) but 90-fold in the cerebellum (obtained with 1 mM SNP). Perfusion with the NO synthase (NOS) inhibitor N G-nitro- l-arginine methyl ester ( l-NAME) suppressed cerebellar cGMP release by 74% indicating that NO is the major regulator of basal cGMP levels in the cerebellum. Quite opposite, l-NAME exhibited no potency in the frontal cortex suggesting that other activators of guanylyl cyclase may regulate basal cortical cGMP levels in vivo.