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The analysis of plasma kinetics of the sympathetic neurotransmitter norepinephrine can be used to estimate sympathetic nervous "activity" (integrated nerve firing rate) for the body as a whole and for individual organs. In 12 patients with cardiac failure (left ventricular ejection fraction 10% to 39%), the mean arterial plasma norepinephrine concentration was 557 + 68 pg/ml (mean SE) compared with 211 + 21 pg/ml in 15 subjects without heart failure (p < .002). The difference was due to both increased release of norepinephrine to plasma (indicating increased "total" sympathetic activity) and reduced clearance of norepinephrine from plasma. The increase in sympathetic activity did not involve all organs equally. Cardiac (32 ± 9 vs 5 ± 1 ng/min; p < .002) and renal (202 ± 45 vs 66 ± 9 ng/min; p = .002) norepinephrine spillover were increased by 540% and 206%, respectively, but norepinephrine spillover from the lungs was normal. Adrenomedullary activity was also increased in the patients with heart failure, whose mean arterial plasma epinephrine concentration was 181 + 38 pg/ml compared with 71 ± 12 pg/ml in control subjects (p < .02). There is marked regional variation, inapparent from measurements of plasma norepinephrine concentration, in sympathetic nerve activity in patients with congestive heart failure. The finding of increased cardiorenal norepinephrine spillover has important pathophysiologic and therapeutic implications. Circulation 73, No. 4, 615421, 1986. THE CONSENSUS that sympathetic nervous overactivity is important in the pathophysiology of congestive heart failure is based in part on observations that the sympathetic neurotransmitter norepinephrine is present in plasma at increased concentration.1 The plasma concentration of norepinephrine, however, is determined by the rates of both release of norepinephrine to plasma and removal of norepinephrine from plasma. Norepinephrine plasma clearance might be reduced, and the plasma concentration thereby increased, because of the reduced cardiac output and organ blood flows that accompany congestive heart failure. A second difficulty in the study of the role of the sympathetic nervous system in congestive heart failure has been the inability of clinical research methods to estimate sympathetic activity in internal organs. Microneurographic electrophysiologic methods are available for the clinical study of nerve firing rates in subcutaneous nerves supplying skin and skeletal muscle,2 but the nerves to internal organs are not accessible for such testing.Measurement of sympathetic transmitter release is an alternative technique for quantifying sympathetic nerve activity in internal organs. We have developed a method3 using infusions of tritiated norepinephrine to determine both the rate at which norepinephrine spills into plasma and its rate of clearance from plasma. The technique has recently been applied to determine the rates of norepinephrine spillover from individual organs.4Although only a small fraction of the norepinephrine

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A number of articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as “promoters” and “amplifiers” of human hypertension. We expand on the role of the sympathetic nervous system in two increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves.

These results suggest that activation of the sympathetic nervous system in patients with heart failure, specifically the cardiac sympathetic nerves, may contribute to the poor prognosis associated with severe heart failure. The data therefore provide a rationale for the use of drugs such as beta-adrenergic blocking agents in the management of patients with heart failure.