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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The cardiovascular effects of nitric oxide and carbon monoxide in the nucleus tractus solitarii of rats.

OBJECTIVE: Nitric oxide (NO) and carbon monoxide (CO) are endogenously synthesized gaseous molecules that act as neurotransmitters in both central and peripheral nervous systems. Previously, we have shown the involvement of NO and CO in central cardiovascular regulation and baroreflex modulation. In this study we investigated the possible interaction of NO and CO in the nucleus tractus solitarii (NTS) on cardiovascular effects in rats. DESIGN AND METHODS: Male Sprague-Dawley rats were anesthetized with urethane, and mean blood pressure (MBP) and heart rate (HR) were monitored intra-arterially. l-Arginine (3.3 nmol), the precursor of NO, or hematin (1 nmol), a heme molecule cleaved by heme oxygenase ( HO) to yield CO, were microinjected unilaterally into the NTS. Cardiovascular effects were evaluated before and after microinjection of the HO inhibitor zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG: 1 nmol) or the NO synthase (NOS) inhibitors N -monomethyl-l-arginine (l-NMMA: 10, 33 and 100 nmol) and N-nitro-l-arginine methyl ester (l-NAME: 10, 33 and 100 nmol). RESULTS: Unilateral microinjection of l-arginine or hematin into the NTS produced decreases in blood pressure and heart rate. These cardiovascular effects of both l-arginine and hematin were attenuated by prior administration of the NOS inhibitors l-NMMA or l-NAME in a dose-dependent manner. However, prior administration of ZnDPBG attenuated only the cardiovascular effects of hematin but not l-arginine. CONCLUSIONS: These results demonstrated that the HO/CO pathway might couple to the activation of NOS via the liberation of NO, to participate in central regulation of cardiovascular function. They also suggested a possible interaction between the NO/NOS and CO/ HO systems in the NTS of rats.[1]


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