Interconversion of O-methylated norepinephrine metabolites in humans

Levo-norepinephrine labeled with tritium was used to study urinary norepinephrine metabolites as an index of whole body norepinephrine turnover. Six healthy volunteers were given intravenous infusions of [ring-2,5,6-3H] levo-norepinephrine, followed by collection of urine for 24 hours. Specific activities were determined by high-performance liquid chromatography for each of the three O-methylated metabolites of norepinephrine in the urine samples, and were then used to calculate the fraction of 4-hydroxy-3-methoxymandelic acid (VMA) formed from 4-hydroxy-3-methoxyphenylglycol (MHPG) and from normetanephrine. These values were used, in conjunction with total excretion of each of these metabolites, to calculate the fraction of MHPG and normetanephrine converted to VMA. The fraction of VMA formed from MHPG was 0.821 +/- 0.020, and that from normetanephrine was 0.179 +/- 0.020. Whereas fractional conversion of normetanephrine to VMA was 0.634 +/- 0.030, that of MHPG to VMA was only 0.507 +/- 0.025. Similar results were obtained when the experiment was repeated in three of the subjects using [8-14C] levo-norepinephrine, suggesting that isotope, specific activity, and position of the label were not determinants of the values obtained. The present results confirm the extent of conversion of MHPG to VMA described by others, and suggest that a higher percentage of normetanephrine than previously reported is converted to VMA.