MAJOR ROLE OF NITRIC-OXIDE IN THE MEDIATION OF REGIONAL CO2 RESPONSIVENESS OF THE CEREBRAL AND SPINAL-CORD VESSELS OF THE CAT

The role of nitric oxide (NO) in the mediation of cerebrovascular CO2 responsiveness was studied in 10 distinct brain and spinal cord region s of the anesthetized, ventilated, temperature-controlled, normoxic ca t. Regional CBF was measured with 15-mu m radiolabeled microspheres in hypocapnic, normocapnic, and hypercapnic conditions. CO2 responsivene ss of each region was determined from the equation of the best-fit reg ression lines to the obtained flow values. The effect of altered endot helial and/or neuronal NO synthesis on CO2 responsiveness was studied following either selective blockade of the NO synthase enzyme by N-ome ga-nitro-L-arginine methyl ester (L-NAME; 3 or 30 mg/kg i.v.) or simul taneous administration of L-NAME (3 mg/kg i.v.) and a large dose of th e NO precursor L-arginine (30 mg/kg i.v.). Blockade of NO synthesis by 30 mg/kg L-NAME resulted in a significant reduction of the steady-sta te regional blood flow values and in an almost complete abolition of t he CO2 sensitivity in each region studied. Changes of the basal flow v alues as well as the reduction of the regional CO2 sensitivity were do se dependent. Hypothalamic, sensorimotor cortical, and cerebellar regi ons were the areas most sensitive to the NO blockade. Impaired CO2 res ponsiveness following NO synthase inhibition, however, was reversed in these regions by simultaneous administration of a large dose of intra venously injected L-arginine. These findings suggest a major role of n itric oxide in the mediation of regional cerebrovascular CO2 responsiv eness in cats.