DETERMINANTS OF CARDIAC TYROSINE-HYDROXYLASE ACTIVITY DURING EXERCISE-INDUCED SYMPATHETIC ACTIVATION IN HUMANS

This study assessed whether the mechanisms regulating cardiac norepine phrine (NE) synthesis with changes in NE release are influenced by fun ctions of sympathetic nerves affecting transmitter turnover independen tly of transmitter release. Differences in arterial and coronary venou s plasma concentrations of NE and its metabolites and of dihydroxyphen ylalanine (DOPA), the immediate product of tyrosine hydroxylase (TH), were examined before and during cycling exercise. Relative increases d uring exercise in cardiac tyrosine hydroxylation (as reflected by the %increase in cardiac DOPA spillover) matched closely corresponding inc reases in NE turnover, but were much lower than increases in NE releas e. The much larger relative increases in release than turnover of NE w ere largely attributable to the extensive contribution to transmitter turnover from intraneuronal metabolism of NE leaking from storage vesi cles. This contribution remains unchanged during sympathetic activatio n so that the relative increase in NE turnover is much smaller than th at in exocytotic release of NE. To replenish the NE lost from stores d uring sympathetic activation, TH activity need increase only in propor tion to the smaller increase in turnover rather than the larger relati ve increase in release. The ability to ''gear down'' increases in tyro sine hydroxylation relative to increases in NE release provides sympat hetic nerves the capacity for a more extended range of sustainable rel ease rates than otherwise possible.