Dopaminergic abnormalities in borderline essential hypertensive patients.
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.
Shigetomi
S
S
Clinical Research Institute of Montreal, Université de Montréal and Hôtel-Dieu de Montréal Hospital, Quebec, Canada.
Buu
N T
NT
Kuchel
O
O
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004295:Dihydroxyphenylalanine / Q000097:blood / Q000494:pharmacology / Q000652:urine; D004298:Dopamine / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D011674:Pulse / Q000187:drug effects; D014443:Tyrosine / Q000097:blood / Q000378:metabolism / Q000652:urine
D014443:Tyrosine; D004295:Dihydroxyphenylalanine; D004298:Dopamine