Effects of sympathetic nerve stimulation on subcellular levels of catecholamine in the heart

Studies were made to determine if neurally induced cardiac catecholamine loss is associated with depletion from a distinct subcellular site. Isolated perfused rabbit hearts with their left and right cardiac accelerans nerves intact were employed. Cardioacceleration was produced by stimulation of either of these nerves anddl-7-H³-norepinephrine, when employed, was administered intravenously 2 hr before removal of the heart from the animal. Following perfusion for 30 min atrial and left ventricular homogenates were prepared and separated into three fractions (coarse, particulate and soluble) by differential centrifugation and the concentration of either endogenous catecholamines ordl-7-H³-norepinephrine was determined in each fraction.Stimulation of the right cardiac accelerans nerve for either 5 or 10 min significantly reduced the concentrations of endogenous catecholamines in the soluble fractions of both atria and the left ventricle; the levels in the particulate fraction remained unchanged. Stimulation of the left cardiac accelerans nerve failed to affect catecholamine levels in any of the fractions studied. Hearts from animals receivingdl-7-H³-norepinephrine exhibited significant depletion of labeled norepinephrine only after 10 min of stimulation of the right cardiac accelerans nerve. This depletion occurred in the soluble fraction of the left ventricle as well as the particulate and soluble fractions of the atria. Depletion of both endogenous catecholamines and labeled norepinephrine (NE) following nerve stimulation could be prevented by the presence of cocaine (40 μg/ml) in the perfusion fluid. These results suggest that stimulation of sympathetic nerves to the heart initially releases catecholamines from the soluble fraction of the cell.