Norepinephrine turnover in peripheral tissues of rats with heart failure

Experiments were performed to determine if there is regional heterogeneity in sympathetic neural activation of peripheral tissues in rats with chronic heart failure (HF; 6-8 wk after coronary artery ligation). Norepinephrine (NE) turnover, an index of sympathetic activation, was determined on the basis of the decline in tissue NE levels that occurs during the 8-h after tyrosine hydroxylase inhibition (α-methyl-DL-p-tyrosine, 300 mg/kg ip at 4-h intervals). Compared with sham-operated rats, NE turnover was increased in the cardiac left ventricle, skeletal muscle, duodenum, and kidney of rats with HF, but was unaltered in liver and spleen. The increased renal NE turnover in HF was largely a reflection of increased turnover in the cortex, with no change evident in the medulla. Blockade of sympathetic ganglionic traffic (hexamethonium, 2 mg/kg sc at 2-h intervals) eliminated the tissue-specific effects of HF on tissue NE levels measured 8-h after tyrosine hydroxylase inhibition. These data support the contention that chronic HF evokes a central nervous system-mediated increase in basal sympathetic tone that exhibits regional heterogeneity (both between and within organs), a phenomenon that likely contributes to the functional consequences of this pathophysiological state.