Serotonin metabolism in the normal and failing hamster heart

Abstract

Serotonin has been found in the heart. Because cardiac serotonin is a potential endogenous source of inotropic support, an understanding of its metabolism in normal and failing hearts may be important. Cardiac serotonin was assayed in cardiomyopathic hamsters and their controls. Hearts were flushed free of platelets. Cardiac serotonin stores were 30-40% of those of norepinephrine. They were not affected by repeated injections of a mast cell granule depletor (H48/80) or the neurotoxins, 6-hydroxydopamine and 5,7-dihydroxytryptamine. Thus, cardiac serotonin appeared to be extraneural and not secondary to mast cell or platelet contamination. Inhibition of serotonin synthesis resulted in a prompt decrease, and inhibition of serotonin degradation led to a rapid increase in cardiac serotonin stores, demonstrating actual serotonin synthesis within the heart. Serotonin content (0.45±0.012 μg/g in controls vs. 0.24±0.009 μg/g in failing myopathic hearts) and synthesis (0.71±0.016 μg/g per hour in controls vs. 0.028±0.011 μg/g per hour in failing myopathic hearts) were significantly reduced in heart failure. Serotonin stores of uterus (a 'control organ') were identical for both strains. There was no difference in cardiac serotonin between the two strains in young hamsters. Human papillary muscles, taken at cardiac surgery, had serotonin levels (0.388±0.027 μg/g) comparable to that found in hamster hearts. Thus, there are significant stores of serotonin synthesized within the heart. Both the stores and synthesis of serotonin are reduced in the failing myopathic hamster heart.