CHRONIC INHIBITION OF NITRIC-OXIDE IN CENTRAL-NERVOUS-SYSTEM DOES NOTCAUSE HYPERTENSION

Acute inhibition of nitric oxide (NO) synthase in the brain causes ele vation of blood pressure and sympathetic excitation under anesthetized conditions. To investigate chronic effects of NO synthase inhibition in the central nervous system on blood pressure regulation in consciou s unrestrained animals, we administered N-G-monomethyl-L-arginine (L-N MMA), a potent NO synthase inhibitor, at low (22.5 mu mol/kg) and high (67.5 mu mol/kg) doses for 1 wk into the cisterna magna with an osmot ic pump and measured mean arterial pressure (MAP) and heart rate (HR) by a telemetry method. The same dose of N-G-monomethyl-D-arginine (D-N MMA), an inactive isomer of L-NMMA, was administered to control rats. Chronic intracisternal administration of low-dose L-NMMA significantly decreased the brain nitrite/nitrate and NO metabolite contents as com pared with D-NMMA (p < 0.05). However, MAP and its variability, HR and its variability, and plasma norepinephrine levels did not differ betw een the two groups of rats at either low- or high-dose treatment. Thus , chronic NO synthase inhibition in the central nervous system did not affect systemic hemodynamics or plasma norepinephrine concentrations despite the inhibition of brain NO. Our results suggest that endogenou s NO in the central nervous system, at least as a whole, may not affec t the systemic hemodynamics of chronic unanesthetized rats.