title: Pressor and sympathoexcitatory effects of nitric oxide in the rostral ventrolateral medulla.
abstract: OBJECTIVE
  It has been shown that nitric oxide (NO) plays an important role in the central control of arterial pressure and sympathetic nerve activity. The aim of this study was to determine whether NO can regulate sympathetic nerve activity by an action on pressor neurons within the rostral part of the ventrolateral medulla (VLM).
  
  
  METHODS
  Experiments were performed on anaesthetized rabbits with denervated arterial and cardiopulmonary baroreceptors. The mean arterial pressure (MAP), heart rate and renal sympathetic nerve activity were measured. Microinjections of the NO donors sodium nitroprusside (SNP, 4-50 nmol) and S-nitroso-glutathione (10 nmol), the NO precursor L-arginine (50 nmol) and the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 50 nmol), were made into the functionally identified pressor region in the rostral VLM. The effects of SNP were also determined before and after injection of 5 nmol methylene blue into the same area. In control experiments, injections of D-arginine (50 nmol) and D-NAME (50 nmol), which are the inactive isomers of L-arginine and L-NAME, respectively, were also made into the functionally identified pressor region in the rostral VLM.
  
  
  RESULTS
  Microinjections of SNP into the rostral VLM pressor region produced a dose-dependent increase in mean arterial pressure and renal sympathetic nerve activity. At the highest dose of 50 nmol, the increase in MAP was 26 +/- 5 mmHg (P < 0.001) and the sympathetic nerve activity was 53 +/- 5% (P < 0.001). These effects were abolished following methylene blue injection into the same region. Injection of 10 nmol S-nitroso-glutathione also produced increases in MAP (15 +/- 2 mmHg, P < 0.001) and in renal sympathetic nerve activity (28 +/- 2%, P < 0.001). Microinjections of L- or D-arginine resulted in very small depressor responses, but had no significant effect on renal sympathetic nerve activity. Microinjections of L-NAME, but not of D-NAME, caused significant decreases in MAP (19 +/- 1 mmHg, P < 0.001) and in sympathetic nerve activity (30 +/- 3%, P < 0.001).
  
  
  CONCLUSIONS
  The results indicate that, in the anaesthetized rabbit with denervated baroreceptors, NO has a pressor and sympathoexcitatory action in the rostral VLM, which is mediated by a cyclic GMP-dependent mechanism. Second, endogenous NO may modulate sympathetic activity tonically, by a direct or indirect action on sympathoexcitatory neurons within the rostral VLM.
authors.affiliation: Department of Physiology, University of Sydney, N.S.W., Australia.
authors.forename: Y
authors.initials: Y
authors.lastname: Hirooka
authors.forename: J W
authors.initials: JW
authors.lastname: Polson
authors.forename: R A
authors.initials: RA
authors.lastname: Dampney
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000294:innervation; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D011817:Rabbits; D026422:S-Nitrosoglutathione; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
chemical_list: D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D009603:Nitroso Compounds; D009599:Nitroprusside; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D019001:Nitric Oxide Synthase; D005978:Glutathione; D019331:NG-Nitroarginine Methyl Ester