Nitric Oxide (NO) partly mediates cerebral hyperemia during hypertension causing pressure-flow passive relationship. We examined whether cerebral hypertension (HiBP) increases cyclic GMP and tested the hypothesis that HiBP increases NO synthase expression in neonatal cerebral microvessels (CMVL). Newborn piglets (age 0-5 days) were given saline (Control,n=8) or L-nitro arginine(LNA 3,000ug/kg, n=8) into lateral ventricles and sagittal sinus and arterial blood samples for cGMP(by RIA) were obtained during two 15 min periods of normotension (N-BP, 90mmHg, produced by an inflated balloon at the descending aorta). cGMP(pg/ml) increased with HiBP (Table) which were not blocked by high doses of LNA suggesting insufficient blockade of NOS or cGMP production from other sites. To determine whether LNA influenced NOS expression, the brains from these piglets were perfused after in-vivo studies for brain and CMVL preparations in Western blots. In the brain, LNA had no effect on endothelial NOS (ecNOS) but completely blocked the inducible (iNOS) and brain(bNOS) isoforms. In contrast, HiBP increased (× 1.5) bNOS expression. LNA completely blocked expression of all NOS isoforms in the CMVL preparation. We conclude that increases in cGMP might be partly due to hypertension-induced over-expression of bNOS which is refractory to LNA.