Analysis of the Sites of Action of Nitric Oxide (NO) in the Central Nervous System : Its Relationship to Central Regulation of Cardiovascular Function

Although nitric oxide (NO) is involved in regulation of the cardiovascular, neuroendocrine, and autonomic system via the central nervous system, its specific sites of action in the brain have not been determined. To clarify the effect of NO in the central nervous system, we injected NO-releasing compounds and NOS inhibitors into the brains of conscious, freely moving rats and measured its effect on mean arterial blood pressure (MAP) and heart rate (HR), as well as on expression of c-fos mRNA, an immediate-early gene used to identify neurons affected by environmental stimuli, and NADPH-diaphorase, an indicator of NOS activity. Intracerebroventricular (icv) administration of the NO donors, 1μmol of sodium nitroprusside (SNP), and NOC-18, caused a significant fall in MAP and HR. In contrast, the NOS inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME), induced a significant rise in MAP when administered either intravenously or intraventricularly. The centrally administered NO donors SNP and NOC-18 induced c-fos mRNA expression in several regions of the brain primarily involved in the baroreceptor response, as well as regions of the brain involved in the integration of autonomic, neuroendocrine, and behavioral responses. Most of the areas that expressed c-fos also stained for NADPH-d. These results suggest that NO acts directly in the brain to reduce the systemic blood pressure, and that the endogenous NO pathway may play a role in cardiovascular and autonomic regulation by modulating neuronal activity in discrete regions of the brain