Central TNF-alpha elevates blood pressure and sensitizes to central pressor action of angiotensin II in the infarcted rats.
In patients with chronic heart failure (CHF) concentration of TNF-alpha is elevated. Enhanced synthesis of TNF-alpha was also found in the hypothalamus of rats shortly after induction of the myocardial infarct. Available evidence indicates that TNF-alpha increases sympathetic activity and enhances function of the renin-angiotensin-aldosterone system in peripheral tissues. The role of TNF-alpha in regulation of the cardiovascular system and its interactions with brain angiotensin II (ANGII) in CHF was evaluated in the following study. Fourteen Sprague-Dawley rats underwent left coronary artery ligation, implantation of lateral cerebral ventricle cannula and insertion of femoral artery catheter. Post-infarct CHF was confirmed by increased left ventricle end-diastolic pressure. Mean arterial blood pressure (MABP) and heart rate (HR) were recorded during 60 min of intracerebroventricular (i.c.v.) infusion of 0.9% NaCl (5 microl/hr) (control group, n = 7) or TNF-alpha (100 ng/5 microl/hr) (experimental group, n = 7). This was followed by i.c.v. injection of subpressor dose of ANGII (5 ng/2 microl/30 sec) and measurements were continued for 20 min. Infusion of TNF-alpha resulted in the increase of MABP without changes in HR. Administration of ANGII elicited significantly greater increase of MABP in rats pretreated with TNF-alpha. Present results indicate that TNF-alpha increases MABP in CHF and sensitizes to pressor effect of centrally administered ANGII.
Zera
T
T
Department of Experimental and Clinical Physiology, Medical University of Warsaw, Poland. tyzer@amwaw.edu.pl
Ufnal
M
M
Szczepanska-Sadowska
E
E
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II