Zera T, Ufnal M, Szczepanska-Sadowska E
Department of Experimental and Clinical Physiology, Medical University of Warsaw, Poland.
J Physiol Pharmacol. 2008 Dec;59 Suppl 8:117-21.
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.
在慢性心力衰竭（CHF）患者中，肿瘤坏死因子-α（TNF-α）的浓度会升高。在大鼠心肌梗死诱导后不久，其下丘脑也发现TNF-α的合成增强。现有证据表明，TNF-α会增加交感神经活动，并增强外周组织中肾素-血管紧张素-醛固酮系统的功能。在以下研究中评估了TNF-α在心血管系统调节中的作用及其与CHF中脑内血管紧张素II（ANGII）的相互作用。十四只Sprague-Dawley大鼠接受了左冠状动脉结扎、侧脑室插管植入和股动脉导管插入。通过左心室舒张末期压力升高来确认梗死后CHF。在脑室内（i.c.v.）输注0.9%氯化钠（5微升/小时）（对照组，n = 7）或TNF-α（100纳克/5微升/小时）（实验组，n = 7）的60分钟内记录平均动脉血压（MABP）和心率（HR）。随后进行脑室内注射低于升压剂量的ANGII（5纳克/2微升/30秒），并持续测量20分钟。输注TNF-α导致MABP升高，而HR无变化。在预先用TNF-α处理的大鼠中，给予ANGII引起的MABP升高明显更大。目前的结果表明，TNF-α会使CHF中的MABP升高，并增强对脑室内给予的ANGII升压作用的敏感性。
