Dopaminergic abnormalities in hypertension associated with moderate renal insufficiency.
To evaluate the additive effect of moderate chronic renal failure to the abnormal dopamine generation and action observed in stable hypertension, we investigated 22 age-matched patients with a comparable degree of hypertension with and without chronic renal failure. Both groups were compared with each other and with an age-matched control group after a single oral dose of dihydroxyphenylalanine (DOPA) while cardiorenal responses and DOPA, dopamine, and their metabolites were measured. The hypertensive patients with chronic renal failure shared with their hypertensive counterparts without chronic renal failure an impaired DOPA decarboxylation to dopamine. However, patients with chronic renal failure had decreased hemodynamic and normal natriuretic responses compared with the hypernatriuresis of hypertensive patients with normal renal function; patients with chronic renal failure had elevated basal plasma concentrations of DOPA and dopamine sulfates as well as increased plasma and urinary DOPA sulfate but blunted urinary dopamine sulfate increases after DOPA administration; they presented augmented plasma atrial natriuretic factor concentrations. Thus, hypertensive patients with moderate chronic renal failure exhibit a decreased hemodynamic responsiveness to DOPA administration-induced dopamine elevation but with the natriuretic effect of dopamine maintained (possibly because of its permissive interaction with increased atrial natriuretic factor levels). Hypertensive patients with chronic renal failure have a heightened DOPA and dopamine sulfoconjugating propensity. Dopamine sulfate attenuates the biologic action of free dopamine. This may contribute (possibly via glomerular hypertension and hyperfiltration due to decreased postglomerular vasodilation) to progressive hypertensive renal damage, particularly in groups predisposed to dopamine deficiency, such as diabetics, blacks, and the elderly.
Kuchel
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Laboratory of the Autonomic Nervous System, Clinical Research Institute of Montreal, Quebec, Canada.
Shigetomi
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000652:urine; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D003404:Creatinine / Q000378:metabolism; D003971:Diastole / Q000187:drug effects; D004295:Dihydroxyphenylalanine / Q000097:blood* / Q000652:urine; D004298:Dopamine / Q000097:blood / Q000652:urine; D005260:Female; D006719:Homovanillic Acid / Q000652:urine; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012964:Sodium / Q000652:urine
D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D009320:Atrial Natriuretic Factor; D012964:Sodium; D003404:Creatinine; D004298:Dopamine; D006719:Homovanillic Acid