Metabolism of endogenous and exogenous noradrenaline in the rabbit perfused heart

The outflow of noradrenaline, 3,4-dihydroxyphenylglycol (DOPEG) and 3,4-dihydroxymandelic acid (DOMA) from rabbit perfused hearts was studied by chromatography on alumina followed by high pressure liquid chromatography with electrochemical detection. In the absence of drugs and without nerve stimulation, the outflow of endogenous noradrenaline over a period of 108 min averaged 0.17 pmol X g-1 X min-1 and the outflow of DOPEG 2.1 pmol X g-1 X min-1. The outflow of DOMA was below the detection limit (less than 0.13 pmol X g-1 X min-1). The effect of perfusion with (-)-noradrenaline 0.1, or 10 mumol/l for 18 min was then investigated. As the concentration of nor-adrenaline increased so did the outflow of DOPEG. Moreover, DOMA was found in the venous effluent during and after perfusion with noradrenaline 1 or 10 mumol/l. The increase in the outflow of DOPEG and DOMA was almost abolished when cocaine 10 mumol/l was present during the perfusion with noradrenaline 1 mumol/l. The release of endogenous noradrenaline by sympathetic nerve stimulation or tyramine 10 mumol/l, but not the release evoked by nicotine 30 mumol/l, was accompanied by an increase in the outflow of DOPEG; an outflow of DOMA was not observed. It is concluded that, in the rabbit perfused heart, DOPEG is an important metabolite of endogenous noradrenaline. DOMA is at best a minor product, either when the neurones are at rest or when noradrenaline is released by sympathetic nerve stimulation, nicotine or tyramine. DOMA is formed in detectable amounts when the tissue is exposed to a high concentration of exogenous noradrenaline. Like DOPEG, it is formed intraneuronally. The results confirm and extend those obtained previously on guinea-pig incubated atria. They make it unlikely that, in these tissues at least, DOMA formation is one of the physiological pathways of noradrenaline catabolism.