Dopaminergic abnormalities in borderline essential hypertensive patients.

Abstract

To explore whether an altered metabolic pathway of dihydroxyphenylalanine (DOPA) may be related to some previously observed dopamine abnormalities in borderline hypertension, we measured basal and DOPA-induced (500 mg orally) changes in blood pressure and pulse rate as well as in three hourly plasma and urine samples. We found that borderline hypertensive patients compared with controls 1) showed a higher baseline urinary excretion of methoxytyramine, a marker of exocytotic dopamine release, with a greater DOPA-induced decrease of systolic blood pressure without reflex tachycardia; 2) had in response to DOPA a blunted plasma DOPA and free dopamine increase but an accentuated plasma dopamine sulfate and urinary DOPAC excretion; and 3) eliminated comparable quantities of dopamine in urine despite a lower rise in the glomerular DOPA load. Furthermore, although DOPA elicited natriuresis in both groups, its effect was greater in borderline hypertensive patients, who lacked the urinary sodium correlation with urinary dopamine excretion seen in control subjects. These data are compatible with increased basal exocytotic dopamine release and accelerated neuronal and renal (extraneuronal) dopamine generation from administered DOPA in borderline hypertension. The DOPA-induced hypernatriuresis exceeding augmented dopamine in borderline hypertensive patients, contrasting with the urinary sodium and dopamine correlation in control subjects, suggests that DOPA induced an additional natriuresis in borderline hypertensive patients by a decrease in renal sympathetic tone because of its central inhibition of sympathetic outflow, which also may account for the absence of reflex tachycardia. {Hyperten-sion 1991;17:997-1002)

Defective dopamine generation from dihydroxyphenylalanine in stable essential hypertensive patients.

“…Moreover, the EH patients were defined only as normal and low renin EH, without respect to other BP characteristics (such as borderline and s-EH), which, in addition to salt sensitivity, 2 proved to be important determinants of the heterogeneity of dopaminergic involvement in EH. 1 We have demonstrated in a previous study 4 that it is possible to detect some hyperdopaminergic patterns in borderline EH patients with measurements of several intermediate steps after an exogenous DOPA-induced increase of circulating DOPA (including metabolites of DOPA, such as 3-O-methyl-DOPA, and of dopamine, such as dopamine sulfate, DOPAC, 3-MT, and HVA in plasma and urine) as well as of renal and vascular responses to dopamine generated from DOPA. Because s-EH patients are closest to those studied earlier, 1 -3 and in contrast to borderline EH characterized by an opposite (i.e., dopaminergic) defect, 2 we extended our investigation to s-EH patients with the oral DOPA test.…”

Peripheral dopamine in hypertension and associated conditions

“…45 It is therefore of interest to compare these patterns to those observed in human hypertension subdivided into borderline and stable. We see in younger borderline hypertensive patients age-matched increases of urinary free DA 46 and 3-MT excretions 47 followed by normal 3-MT 48 or lower furosemide stimulated urinary DA excretion and natriuresis in older age-matched stable hypertensive patients. 46 Probably compensatory hyperdopaminergic patterns in initial stages of hypertension, subsequently confirmed in SHR 49 and in young borderline hypertensive patients, 50 are associated with a decreased natriuretic response to exogenous DA in SHR.…”

“…When comparing age-matched controls, borderline and stable hypertensive patients (lower panel, right) control subjects have an increase in urinary 3-methoxytyramine excretion with age. Considering this age-dependent increase, urinary 3-methoxytyramine excretion was found to be increased only in the younger borderline 47 but not older stable hypertensive patients. 48 tory to the tubular receptor defect.…”

“…basal exocytotic DA release probably preceded by accelerated DA generation from DOPA, 47 accentuated by D␤H suppression 54 and reflected by increased urinary DA excretion. 46,50 Non-modulating hypertensives who are mostly borderline were found to have increased plasma free DA.…”

“…The hyperdopaminergic features of borderline hypertension 46,47,50 remain unexplained. With hypertension progressing into the stable form, the dopaminergic activity is weakening.…”