RESTORATION OF CARDIAC RESPONSIVENESS TO TYRAMINE AFTER RESERPINE

¹ Department of Pharmacology, College of Medical Sciences, University of Minnesota, Minneapolis, Minnesota

The return of responsiveness of isolated perfused cat hearts to tyramine was determined at several intervals after pretreatment with reserpine in vivo. At 9 days but not at 7 days after reserpine the magnitude of the increase in coronary flow and in heart rate produced by tyramine was equal to that of control hearts. Although endogenous norepinephrine (NE) levels were still significantly depressed at 9 days after reserpine, the percentage of NE present in the soluble fraction of ventricular homogenates was greater than in control hearts, yet the concentration of NE in this fraction was still significantly less than normal. Tracer doses of dl-7-H³-norepinephrine (H³-NE) were taken up and retained normally in hearts 9 days after reserpine, but not at 7 days, although the subcellular distribution of H³-NE at both 7 and 9 days after reserpine administration was not significantly different from that of control hearts. The capacity of tyramine to release cardiac H³-NE in vitro had returned to normal at 9 days, but was still significantly depressed at 7 days after reserpine. There was no alteration in the rate of release of H³-NE or its O-methylated metabolites during control perfusion time periods. The results indicate that the return of normal cardiac responsiveness to tyramine in vitro correlates most closely with the capacity of the heart to store H³-NE in vivo and to release H³-NE in vitro. These results support the view that the neurotransmitter store of NE concerned with the sympathomimetic response to tyramine represents only a small fraction of the total NE stores.