title: Nitric oxide signaling pathway mediates the L-arginine-induced cardiovascular effects in the nucleus tractus solitarii of rats.
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.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: H C
authors.initials: HC
authors.lastname: Lin
authors.forename: F J
authors.initials: FJ
authors.lastname: Wan
authors.forename: K K
authors.initials: KK
authors.lastname: Cheng
authors.forename: C J
authors.initials: CJ
authors.lastname: Tseng
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002319:Cardiovascular System / Q000187:drug effects*; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007191:Indazoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D052248:Nitric Oxide Synthase Type I; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D017552:Solitary Nucleus / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D012995:Solubility; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000634:Aminoquinolines; D002147:Calmodulin; D007191:Indazoles; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D009569:Nitric Oxide; C017967:W 7; C041715:6-anilino-5,8-quinolinedione; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D011494:Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D002118:Calcium; C080122:7-nitroindazole