title: Centrally administered TNF increases arterial blood pressure independently of nitric oxide synthase.
abstract: BACKGROUND
  Emerging evidence indicates that increased levels of TNF in the brain are associated with hypertension. Nitric oxide synthase (NOS) is involved in the central control of the cardiovascular system, exerting both pro- and antihypertensive effects. TNF induces hypothalamic synthesis of nitric oxide.
  
  
  OBJECTIVE
  We checked if acutely administered TNF into the cerebral ventricles affects arterial blood pressure, heart rate and baroreflex sensitivity, and whether TNF actions are dependent on NOS in normotensive rats.
  
  
  METHODS
  We carried out hemodynamic measurements in 6 groups of freely moving, adult Sprague-Dawley male rats, intracerebroventricularly (ICV) infused with either: 1) saline (5μl/h); 2) TNF (200ng/5μl/h); 3) non-selective NO synthase inhibitor - l-NG-Nitroarginine Methyl Ester (l-NAME) (1mg/5μl/h); 4) TNF together with l-NAME (200ng and 1mg/5μl/h, respectively); 5) neuronal NO synthase inhibitor - 7-nitroindazole sodium salt (7-NI) (20μg/10μl/h); 6) or TNF together with 7-NI (200ng and 20μg/10μl/h, respectively). Mean arterial blood pressure (MABP), heart rate (HR) and spontaneous baroreflex sensitivity (sBRS) evaluated by the sequence method were analysed.
  
  
  RESULTS
  ICV infusion of TNF caused a significant increase in MABP accompanied by a transient increase in HR, and a decrease in sBRS. ICV infusion of l-NAME increased MABP, but it did not change HR, nor sBRS. ICV infusion of 7-NI did not affect MABP, nor HR, nor sBRS. TNF administered together with l-NAME increased MABP with a transient increase in HR without changes of sBRS. Similarly, ICV infusion of TNF with 7-NI increased MABP without changes in HR and sBRS.
  
  
  CONCLUSIONS
  Centrally administered TNF increases MABP and HR and blunts sBRS. The pressor effect of TNF appears to be independent of NOS activity in the brain. Inhibition of nNOS restores sBRS in TNF treated rats.
authors.affiliation: Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, The Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland. Electronic address: tzera@wum.edu.pl.
authors.forename: Tymoteusz
authors.initials: T
authors.lastname: Żera
authors.affiliation: Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, The Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Nowiński
authors.affiliation: Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, The Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kwiatkowski
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects*; D017704:Baroreflex / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester
keywords: Baroreflex sensitivity; Blood pressure; Brain; Cytokine; Nitric oxide synthase; Tumor necrosis factor