title: TNF and angiotensin type 1 receptors interact in the brain control of blood pressure in heart failure.
abstract: Accumulating evidence suggests that the brain renin-angiotensin system and proinflammatory cytokines, such as TNF-α, play a key role in the neurohormonal activation in chronic heart failure (HF). In this study we tested the involvement of TNF-α and angiotensin type 1 receptors (AT1Rs) in the central control of the cardiovascular system in HF rats.
  
  
  METHODS
  we carried out the study on male Sprague-Dawley rats subjected to the left coronary artery ligation (HF rats) or to sham surgery (sham-operated rats). The rats were pretreated for four weeks with intracerebroventricular (ICV) infusion of either saline (0.25μl/h) or TNF-α inhibitor etanercept (0.25μg/0.25μl/h). At the end of the pretreatment period, we measured mean arterial blood pressure (MABP) and heart rate (HR) at baseline and during 60min of ICV administration of either saline (5μl/h) or AT1Rs antagonist losartan (10μg/5μl/h). After the experiments, we measured the left ventricle end-diastolic pressure (LVEDP) and the size of myocardial scar.
  
  
  RESULTS
  MABP and HR of sham-operated and HF rats were not affected by pretreatments with etanercept or saline alone. In sham-operated rats the ICV infusion of losartan did not affect MABP either in saline or in etanercept pretreated rats. In contrast, in HF rats the ICV infusion of losartan significantly decreased MABP in rats pretreated with saline, but not in those pretreated with etanercept. LVEDP was significantly elevated in HF rats but not in sham-operated ones. Surface of the infarct scar exceeded 30% of the left ventricle in HF groups, whereas sham-operated rats did not manifest evidence of cardiac scarring.
  
  
  CONCLUSIONS
  our study provides evidence that in rats with post-infarction heart failure the regulation of blood pressure by AT1Rs depends on centrally acting endogenous TNF-α.
authors.affiliation: Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, The Medical University of Warsaw, Banacha 1B Str., 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 Str., 02-097 Warsaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Ufnal
authors.affiliation: Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, The Medical University of Warsaw, Banacha 1B Str., 02-097 Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Szczepańska-Sadowska
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism*; D002490:Central Nervous System; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006339:Heart Rate; D006439:Hemodynamics; D008297:Male; D009995:Osmosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D012084:Renin-Angiotensin System; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D014409:Tumor Necrosis Factor-alpha
keywords: Angiotensin type 1 receptors (AT1Rs); Blood pressure; Central nervous system; Heart failure; Tumor necrosis factor alpha (TNF-α)