Biochemical Basis of Heart Function. III. Influence of Isoproterenol on the Norepinephrine Stores in the Rat Heart

Abstract

A single subcutaneous injection of isoproterenol into rats markedly reduced the concentration of norepinephrine (NE) in their hearts, but doses greater than 20 mg/kg failed to decrease NE levels below 30–40% of the control value. Restoration of lost NE began more than 48 h after injection of the isoproterenol and was not complete in 96 h. Twenty-four hours after treatment with isoproterenol the pattern of subcellular distribution of the NE in the heart was not altered from the controls, but 96 h after treatment the NE concentration had decreased in the granular fraction and increased in the soluble fraction. Isoproterenol failed to decrease NE levels in other adrenergically innervated organs such as spleen and brain. Subcutaneous doses (1 mg/kg) of NE and epinephrine also reduced the cardiac NE in the control animals but did not further reduce the NE stores in the hearts of isoproterenol-treated rats. A second injection of isoproterenol (20 mg/kg) also failed to further decrease the NE stores in the hearts of isoproterenol-treated animals. On the other hand, tyramine treatment or exposure of the rats to cold (4 °C) for 4 h lowered the cardiac endogenous NE in both the control and isoproterenol-treated animals. Pretreatment of rats with TM-10, tranylcypromine, dibenamine, and propranolol failed to prevent the isoproterenol-induced decrease in cardiac NE stores. The data reveal that isoproterenol-resistant norepinephrine stores in the heart are susceptible to the action of tyramine or cold exposure, and the isoproterenol-induced alteration in catecholamine stores may not be the result of a direct action of this agent on the adrenergic nerve terminal.