Major Role of Nitric Oxide in the Mediation of Regional CO 2 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 regions of the anesthetized, ventilated, temperature-controlled, normoxic cat. Regional CBF was measured with 15-μm radiolabeled microspheres in hypocapnic, normocapnic, and hypercapnic conditions. CO₂ responsiveness of each region was determined from the equation of the best-fit regression lines to the obtained flow values. The effect of altered endothelial and/or neuronal NO synthesis on CO₂ responsiveness was studied following either selective blockade of the NO synthase enzyme by N^ω-nitro-L-arginine methyl ester (L-NAME; 3 or 30 mg/kg i.v.) or simultaneous administration of L-NAME (3 mg/kg i.v.) and a large dose of the 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-state regional blood flow values and in an almost complete abolition of the CO₂ sensitivity in each region studied. Changes of the basal flow values as well as the reduction of the regional CO₂ sensitivity were dose dependent. Hypothalamic, sensorimotor cortical, and cerebellar regions were the areas most sensitive to the NO blockade. Impaired CO₂ responsiveness following NO synthase inhibition, however, was reversed in these regions by simultaneous administration of a large dose of intravenously injected L-arginine. These findings suggest a major role of nitric oxide in the mediation of regional cerebrovascular CO₂ responsiveness in cats.