Chronic inhibition of nitric oxide in central nervous system does not cause hypertension

Abstract

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 NG-monomethyl-L-arginine (L-NMMA), a potent NO synthase inhibitor, at low (22.5 μmol/kg) and high (67.5 μmol/kg) doses for 1 wk into the cisterna magna with an osmotic pump and measured mean arterial pressure (MAP) and heart rate (HR) by a telemetry method. The same dose of NG-monomethyl-D-arginine (D-NMMA), 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 compared with D-NMMA (p<0.05). However, MAP and its variability, HR and its variability, and plasma norepinephrine levels did not differ between 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 endogenous NO in the central nervous system, at least as a whole, may not affect the systemic hemodynamics of chronic unanesthetized rats.