Augmented Sympathetic Neurotransmitter Activity in the Peripheral Vascular Bed of Patients with Congestive Heart Failure and Cardiac Norepinephrine Depletion

Abstract

Since there is an overall augmentation of sympathetic nervous activity in patients with congestive heart failure while adrenal medullary function is normal and neurotransmitter stores are diminished in the heart, investigation was directed to the functional status of adrenergic receptors and available norepinephrine stores in the peripheral vascular beds. Blood flow, determined plethysmographically, and vascular resistance, calculated in the calf, following intra-arterial injections of tyramine and norepinephrine in eight patients with congestive heart failure were compared to the responses in nine patients with heart disease but without heart failure. The absolute increase in vascular resistance produced by graded doses of norepinephrine was greater in patients with heart failure. However, the relative augmentation of vascular resistance produced by any dose of norepinephrine was essentially identical in the two groups. In contrast, the vasoconstrictor response to a standard dose of the indirectly acting sympathomimetic agent, tyramine, was markedly enhanced (P<0.01) in cases of heart failure, both when this increased response was considered in terms of the relative rise in vascular resistance, and in the quantity of injected norepinephrine required to produce a similar elevation of resistance. Concentration of norepinephrine in atrial tissue, determined at the time of cardiac surgery a few days after completion of the pharmacological studies, was significantly lower in the patients with heart failure. It is concluded that the quantity of endogenous sympathetic neurotransmitter available for release by tyramine from nerve endings in the peripheral arteriolar bed in the calf is not reduced and may even be augmented in patients with heart failure, and that the elevated levels of plasma norepinephrine in the heart failure state are derived, at least in part, from labile adrenergic stores in the peripheral vascular bed.