Key result
MAO inhibitors reduce oxidative deamination, the dominant noradrenaline metabolism pathway in human saphenous veins.
The human saphenous vein metabolizes exogenous noradrenaline primarily through oxidative deamination, a pattern differing from other animal species.
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Questions reliance on animal data for human venous noradrenaline metabolism; leaves open therapeutic implications of MAO inhibition.
Human saphenous vein segments were obtained from patients subjected to coronary bypass surgery. As determined by HPLC-ED, the veins had a relatively low content of noradrenaline and high content of the deaminated metabolites, dihydroxyphenylglycol (DOPEG) and dihydroxymandelic acid (DOMA). In vein segments which had been incubated with 3H-noradrenaline (0.1 mumol/l), the oxidative deamination pathway predominated over the O-methylating one. Deamination occurred both at the neuronal and extraneuronal level; DOPEG appearing to be a good index of intraneuronal deamination, whereas DOMA and O-methylated and deaminated metabolites were mainly formed extraneuronally. Both MAO type A and MAO type B selective inhibitors reduced the deamination of noradrenaline; deamination was also found to be partially sensitive to semicarbazide. Inhibition of neuronal uptake or of deamination increased O-methylation. The human saphenous vein thus metabolizes exogenous noradrenaline following a pattern which substantially differs from that shown to occur in various blood vessels from other animal species.
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Branco et al. (1992) studied Patients subjected to coronary bypass surgery. 3H-noradrenaline and MAO inhibitors was evaluated on Metabolism of exogenous noradrenaline. In human saphenous vein segments, the oxidative deamination pathway predominated over O-methylation for exogenous noradrenaline metabolism, which was reduced by MAO type A and B selective inhibitors.
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