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  • Title: Nitric oxide signaling pathway mediates the L-arginine-induced cardiovascular effects in the nucleus tractus solitarii of rats.
    Author: Lin HC, Wan FJ, Cheng KK, Tseng CJ.
    Journal: Life Sci; 1999 Oct 29; 65(23):2439-51. PubMed ID: 10622228.
    Abstract:
    We have previously demonstrated that L-arginine produces profound cardiovascular effects when microinjected into the nucleus tractus solitarii (NTS) of the rat. The present study extended our earlier work and examined further the underlying mechanisms of action of L-arginine in the NTS. Our results showed that intra-NTS microinjection of L-arginine (0.1-10 nmol) elicited dose-dependent depressor and bradycardic effects that were not significantly evoked by equivalent doses of D-arginine. The effects of L-arginine were blocked by pre-injection of 7-nitroindazole (0.02-1 nmol), a neuronal nitric oxide synthase inhibitor. Additionally, application of the calmodulin inhibitor W-7 (0.01-0.33 nmol) reduced cardiovascular responses to L-arginine (10 nmol) in a dose-dependent manner. Pre-injections of soluble guanylyl cyclase inhibitors, LY83583 (0.01-0.33 nmol) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 0.03-1 pmol) both suppressed the L-arginine-induced depressor and bradycardic effects. Finally, the cardiovascular effects of L-arginine in the NTS were attenuated by HA1004 (0.1-1 nmol), a cGMP-dependent protein kinase inhibitor, but not by the protein kinase C inhibitor H-7 (1 nmol). Taken together, the results indicate that the cardiovascular effects produced by L-arginine in the NTS are inhibited by pharmacological interventions that block nitric oxide production and cGMP-PKG signaling pathway within the nucleus.
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