Dissociation of biochemical and hypotensive effects of debrisoquine in hypertensive patients.

The 24 h urinary excretion of adrenaline, noradrenaline, metadrenaline, normetadrenaline and vanillylmandelic acid, plasma renin activity and plasma and urinary debrisoquine were measured before and during chronic treatment with oral debrisoquine in 14 in-patients with essential hypertension. There was a significant fall (mean +/- SD) in the 24 h urinary excretion of vanillylmandelic acid (15.3 +/- 2.8 to 6.7 +/- 1.9 micronmol) noradrenaline (199.0 +/- 105.8 to 125.2 +/- 43.3 nmol) and plasma renin activity (0.71 +/- 0.47 to 0.40 +/- 0.20 pmol Angio I ml-1 h-1) while the urinary normetadrenaline/noradrenaline ratio increased (10.4 +/- 6.1 to 17.1 +/- 5.1). No significant change was seen in the output of adrenaline or of O-methylated metabolites. Debrisoquine produces extensive noncompetitive inhibition of platelet monoamine oxidase in vivo at low therapeutic plasma concentrations. These changes support the view that treatment with debrisoquine produces intraneuronal inhibition of monoamine oxidase and post-ganglionic blockage. There was a significant correlation between the change in standing diastolic blood pressure and the daily dose (rs = -0.52), pre-dose plasma concentration (rs = -0.85) and mean daily urinary recovery (rs = -0.80), of debrisoquine. The full extent of the biochemical changes were seen at low dose and low plasma concentration and were not directly correlated with the fall in standing or supine blood pressure.

The urinary excretion of catecholamines and their derivatives in primary hypertension in man.

1. The 24 h urinary excretion of adrenaline, noradrenaline, normetadrenaline, metadrenaline and vanilloylmandelic acid has been compared in 17 male normotensive subjects and 25 age-matched male hypertensive patients studied under similar in-patient conditions. 2. 24 h urinary metadrenaline was significantly lower in the hypertensive patients. With this exception, no significant differences were found between the two groups when the total 24 h excretion of free catecholamines and their metabolites was analysed. 3. Diurnal variation in free catecholamine excretion was found in both normotensive and hypertensive subjects. There was no corresponding variation in metabolite excretion. 4. No correlation could be established between systolic or diastolic blood pressure and the amounts of the catecholamines or their metabolites in the urine of either group. 5. The results are considered in the light of recent work demonstrating high plasma catecholamine concentrations in hypertension. They lend no support to the concept that excessive circulating catecholamines are responsible for the elevated blood pressure in essential hypertension.