DOPAMINERGIC ABNORMALITIES IN HYPERTENSION ASSOCIATED WITH MODERATE RENAL-INSUFFICIENCY

To evaluate the additive effect of moderate chronic renal failure to t he abnormal dopamine generation and action observed in stable hyperten sion, we investigated 22 age-matched patients with a comparable degree of hypertension with and without chronic renal failure. Both groups w ere compared with each other and with an age-matched control group aft er a single oral dose of dihydroxyphenylalanine (DOPA) while cardioren al 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 D OPA decarboxylation to dopamine. However, patients with chronic renal failure had decreased hemodynamic and normal natriuretic responses com pared with the hypernatriuresis of hypertensive patients with normal r enal function; patients with chronic renal failure had elevated basal plasma concentrations of DOPA and dopamine sulfates as well as increas ed plasma and urinary DOPA sulfate but blunted urinary dopamine sulfat e increases after DOPA administration; they presented augmented plasma atrial natriuretic factor concentrations. Thus, hypertensive patients with moderate chronic renal failure exhibit a decreased hemodynamic r esponsiveness to DOPA administration-induced dopamine elevation but wi th the natriuretic effect of dopamine maintained (possibly because of its permissive interaction with increased atrial natriuretic factor le vels). Hypertensive patients with chronic renal failure have a heighte ned DOPA and dopamine sulfoconjugating propensity. Dopamine sulfate at tenuates the biologic action of free dopamine. This may contribute (po ssibly via glomerular hypertension and hyperfiltration due to decrease d postglomerular vasodilation) to progressive hypertensive renal damag e, particularly in groups predisposed to dopamine deficiency, such as diabetics, blacks, and the elderly.