Sympathoexcitation in heart failure-Norepinephrine kinetics in sympathetic nerve terminals.

交感神经活动增加与心力衰竭患者的高死亡率和发病率相关。β-肾上腺素受体阻滞剂或血管紧张素转换酶抑制剂诱导的交感神经痛可改善心室功能和死亡率。先前的研究表明，尽管心脏组织中去甲肾上腺素（NE）含量显著降低，但心力衰竭时心脏NE溢出增加，即，交感神经末梢的减少因此，衰竭心脏交感神经末梢中的NE动力学尚未完全了解。因此，我们研究了高血压性心力衰竭发生发展过程中心室功能和心肾间质NE水平的变化。在DS大鼠中，高盐饮食导致12周龄时血压升高和代偿性肥大的发展，导致18周时心力衰竭。在con ...更多信息 相反，DR大鼠没有发生高血压或肥大。微透析法测定间质NE水平。与相应的DR大鼠相比，12周和18周DS大鼠心脏NE含量显著降低。心脏间质NE的水平在DS大鼠不变，尽管肥厚或心力衰竭的发展，并没有从相应的DR大鼠不同。然而，升高间质NE诱导静脉注射酪胺在DS大鼠延长12和18周龄。结果提示，高血压性心力衰竭时心、肾交感神经元功能障碍，在精神和躯体应激引起交感神经兴奋后，肾间质NE水平持续升高，导致心力衰竭进展。少

Increases in sympathetic nerve activity are associated with high mortality and morbidity in patients with heart failure. Sympathoinlhibition induced by beta-adrenoceptor blockade or angiotensin-converting enzyme inhibitor improves ventricular function and mortality. Previous studies have shown increased cardiac norepinephrine (NE) spillover in heart failure despite marked reduction in NE contents of cardiac tissue, i.e., its reduction in sympathetic nerve terminals. Thus, NE kinetics in sympathetic nerve terminals of failing hearts is not fully understood. Accordingly, we investigated ventricular function and interstitial NE levels of heart and kidney during the development of hypertensive heart failure.Dah1 salt-sensitive (DS) and salt-resistant (DR) rats were fed a diet containing 8% NaCl after the age of 6 weeks. In DS rats, high-salt diet resulted in increasing blood pressure and development of compensated hypertrophy at 12 weeks of age, leading to heart failure by 18 weeks. In con … More trast, DR rats did not develop hypertension or hypertrophy. Levels of interstitial NE were determined by microdialysis method. Cardiac NE contents were markedly reduced in DS rats of 12 and 18 weeks, as compared to each corresponding DR rats. Levels of cardiac interstitial NE in DS rats were unchanged despite the development of hypertrophy or heart failure and were not different from those of the corresponding DR rats. However, an elevation of interstitial NE induced by intravenous injection of tyramine in DS rats was prolonged in 12 and 18 weeks of age. Levels of renal interstitial NE was greater at 18-week DS rats before tyramine and the elevation by tyramine was markedly prolonged in the kidney of 18-week DS rats.These results suggest that cardiac and renal sympathetic neuronal dysfunction in hypertensive heart failure results in prolonged elevation of their interstitial NE levels after sympathetic nerve excitation induced by mental and physical stress, leading to progressing in heart failure. Less