title: Neuronal nitric oxide reduces sympathetic excitability by modulation of central glutamate effects in pigs.
abstract: Mechanisms of the modulation of sympathetic activity by neuronal NO were studied in vagotomized anesthetized pigs. Inhibition of neuronal NO synthase (nNOS) within the brain stem by intracerebroventricular (ICV) administration of 7-nitroindazole (7-NI, 1 mmol/L) or S-methyl-L-thiocitrulline (MeTC, 0.1 mmol/L) caused slight increases in renal sympathetic nerve activity (RSNA) but did not affect arterial blood pressure (BP) or cardiac output (CO). However, the sympathoexcitatory effects of glutamate (0.5 mL, 0.1 mol/L ICV) that were associated with marked increases in BP, CO, and heart rate were potentiated by both nNOS inhibitors. Furthermore, 7-NI and MeTC significantly enhanced the responses of RSNA, BP, and CO to activation of somatosympathetic reflexes via stimulation of the left greater sciatic nerve (nervus ischiadicus, 10 to 20 V, 30 Hz, 1-millisecond pulses). Subsequent systemic inhibition of either the neuronal (by 7-NI) or all isoforms of NOS by NG-nitro-L-arginine-methyl ester (20 mg/kg) had no significant additional effects on these responses. The effects of NOS inhibition were effectively counteracted by the endogenous NOS substrate L-arginine and by S-nitroso-N-acetyl-penicillamine (SNAP), a stable analogue of endogenous S-nitroso factors. Disruption of sympathoinhibitory baroreflex mechanisms by bilateral cutting of the carotid sinus nerves caused increases in RSNA and slightly increased responses to all excitatory stimuli but had no effects on the actions of the NOS inhibitors or SNAP. These results suggest that modulation of glutamate effects by nNOS-derived NO may be an important mechanism by which NO affects sympathetic activity in pigs.
authors.affiliation: I. Physiologisches Institut, Universität Heidelberg, Germany. zanzing@novsrv1.pio1.uni-heidelberg.de
authors.forename: J
authors.initials: J
authors.lastname: Zanzinger
authors.forename: J
authors.initials: J
authors.lastname: Czachurski
authors.forename: H
authors.initials: H
authors.lastname: Seller
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects; D002956:Citrulline / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000187:drug effects / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007191:Indazoles / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D013552:Swine; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014628:Vagotomy
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D019335:Nitroarginine; D002956:Citrulline; D009569:Nitric Oxide; D018698:Glutamic Acid; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D019001:Nitric Oxide Synthase; D010396:Penicillamine; D013890:Thiourea; C086717:S-methylthiocitrulline; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester