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

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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