title: Defective 3,4-dihydroxyphenylalanine decarboxylation to dopamine in hydralazine-treated hypertensive patients may be pyridoxine remediable.
abstract: The previously observed defective dopamine (DA) generation from 3,4-dihydroxyphenylalanine (DOPA) can also be seen in patients treated for many years by hydralazine. This may be due to a hydralazine-induced depletion of pyridoxine, an essential coenzyme of the aromatic L-amino acid decarboxylase (LAAD). Eleven hydralazine-treated stable essential hypertensive (EH) patients, initially found to have a defect in the DOPA decarboxylation to DA, tested by a single DOPA administration (500 mg, orally), were retested by the same test 4 days after pyridoxine pretreatment (100 mg/day) for data on blood pressure (BP), pulse rate, and renal and plasma catecholamines and their metabolites, as well as plasma atrial natriuretic factor (ANF), cyclic GMP (cGMP), plasma renin activity (PRA), and plasma aldosterone (PA). Initially, hydralazine-treated stable EH patients manifested, following DOPA administration, lower DOPA decarboxylation to DA than control subjects. Pyridoxine pretreatment accelerated DA generation from exogenous DOPA and attenuated the DOPA-induced increases in plasma and urinary DOPA and its metabolite 3-O-methyl-DOPA, but accentuated the increase in free DA and its main metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), while BP, ANF, cGMP, PRA, and PA remained unaffected. The DOPA-induced increments of urinary DA were, in contrast to plasma DA changes, blunted by pyridoxine pretreatment. The attenuation of the sodium excretion by pyridoxine pretreatment exceeded that of the DA excretion, suggesting that pyridoxine suppressed a natriuretic factor, other than ANF, or activated a sodium-retaining factor, other than renin or aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Clinical Research Institute of Montréal, Québec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Shigetomi
authors.forename: O
authors.initials: O
authors.lastname: Kuchel
mesh_terms: D000328:Adult; D002319:Cardiovascular System / Q000187:drug effects; D003653:Decarboxylation / Q000187:drug effects; D004295:Dihydroxyphenylalanine / Q000097:blood / Q000378:metabolism* / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D004298:Dopamine / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D006830:Hydralazine / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects; D007980:Levodopa; D008297:Male; D008875:Middle Aged; D011736:Pyridoxine / Q000627:therapeutic use*; D012964:Sodium / Q000378:metabolism
chemical_list: D006728:Hormones; D006830:Hydralazine; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D012964:Sodium; D011736:Pyridoxine; D004298:Dopamine