title: Nitric oxide within the paraventricular nucleus mediates changes in renal sympathetic nerve activity.
abstract: The paraventricular nucleus (PVN) of the hypothalamus is known to be involved in the control of sympathetic outflow. The goal of the present study was to examine the role of nitric oxide within the PVN in the regulation of renal sympathetic nerve activity. Renal sympathetic nerve discharge (RSND), arterial blood pressure, and heart rate in response to the microinjection of nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 50, 100, and 200 pmol) into the PVN were measured in male Sprague-Dawley rats. Microinjection of L-NMMA elicited an increase in RSND, arterial blood pressure, and heart rate. Administration of NG-monomethyl-D-arginine (D-NMMA, 50-200 pmol) into the PVN did not change RSND, arterial pressure, or heart rate. Similarly, microinjection of another nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 100 nmol) also elicited an increase in RSND, arterial blood pressure, and heart rate. L-Arginine (100 nmol) reversed the effects of L-NAME in the PVN. Furthermore, microinjection of sodium nitroprusside (SNP; 50, 100, and 200 nmol) into the PVN elicited a significant decrease in RSND, arterial blood pressure, and heart rate. These effects of L-NMMA, L-NAME, and SNP on RSND and arterial blood pressure were not mediated by their vasoactive action because microinjection of phenylephrine and hydralazine did not elicit similar respective changes. In conclusion, our data indicate that endogenous nitric oxide within the PVN regulates sympathetic outflow via some inhibitory mechanisms. Altered nitric oxide mechanisms within the PVN may contribute to elevated sympathetic nerve activity observed during various diseases states such as heart failure and hypertension.
authors.affiliation: Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198, USA.
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.forename: W G
authors.initials: WG
authors.lastname: Mayhan
authors.forename: K P
authors.initials: KP
authors.lastname: Patel
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001931:Brain Mapping; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D007668:Kidney / Q000294:innervation*; D008297:Male; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D009599:Nitroprusside; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester