Defective dopamine generation from dihydroxyphenylalanine in stable essential hypertensive patients.
We studied the metabolic pathways of dihydroxyphenylalanine (DOPA) and dopamine as well as the cardiovascular and renal responses to a single administration of DOPA (500 mg orally) in stable essential hypertension. We found that after DOPA, stable hypertensive patients compared with controls showed more blood pressure decrease without reflex tachycardia, had lower creatinine clearance but a higher fractional excretion of sodium, and had lower plasma renin activity at the height of DOPA action. Hypertensive patients also showed increased plasma DOPA, the ratio of plasma DOPA to dopamine, and the sum of plasma DOPA and 3-O-methyl-DOPA, as well as increased urinary 3-O-methyl-DOPA and the plasma and urine dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid. Finally, despite an augmented post-DOPA glomerular load of DOPA, the predominant source of urinary dopamine, the excretion rates of dopamine and its metabolites remained comparable in hypertensive patients to those in control subjects. These data suggest that, in stable hypertensive patients, exogenous DOPA is to a lesser degree decarboxylated to dopamine, which is more rapidly metabolized intraneuronally. Contrasting with this finding are the hyperdopaminergic features, such as hypernatriuresis with renin suppression and excessive blood pressure decline in the absence of reflex tachycardia. They may be due to an upregulation of renal, vascular, and brain dopaminergic receptors secondary to a preexisting dopaminergic deficiency in stable essential hypertension.
Kuchel
O
O
Clinical Research Institute of Montreal, Quebec, Canada.
Shigetomi
S
S
D000284:Administration, Oral; D001794:Blood Pressure / Q000187:drug effects; D004295:Dihydroxyphenylalanine / Q000378:metabolism* / Q000494:pharmacology; D004298:Dopamine / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011674:Pulse / Q000187:drug effects; D014443:Tyrosine / Q000097:blood
D014443:Tyrosine; D004295:Dihydroxyphenylalanine; D004298:Dopamine