Role of brain nitric oxide in the development of experimental hypertension.

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Acute inhibition of nitric oxide (NO) synthase in the brain causes elevation 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 conscious unrestrained animals, we administered N^G-monomethyl-L-arginene (L-NMMA), a potent NO synthase inhibitor at low (22.5mumol/kg) and high (67.5mumol/kg) doses for one week into the cisterna magna by an osmotic pump, while measuring mean arterial pressure (MAP) and heart rate (HR) by a telemetry method. The same dose of N^G-monomethyl-D-arginine (D-NMMA), an inactive isomer of L-NMMA,was administered into control rats. Chronic intracisternal administration of low dose L-NMMA significantly decreased the brain nitrite/nitrate, NO metabolites, content compared with that of D-NMMA (p<05). However, MAP and its variability, HR and its variability and plasma norepinephrine levels were not different between two groups of rats with either low or high dose treatment. Thus, chronic NO synthase inhibition in the central nervous system did not affect systemic hemodynamics and plasma norepinephrine concentrations in spite of the inhibition of brain NO.Our results suggest that endogenous NO in the central nervous system may not have effects on systemic hemodynamics of chronic unanesthetized rats.