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. {Hypertension 1991;17:997-1002)Human essential hypertension is a family of diseases; one subtype has an increased maximum velocity for red blood cell lithium-sodium countertransport activity. To begin the localization of the gene or genes responsible for this phenotype, we examined the association of blood pressure, lithium-sodium countertransport, and two genetic markers previously associated with hypertension ‐ the MN blood group antigen (chromosome 4) and the plasma protein haptoglobin (chromosome 18) ‐ in a population-based sample of 592 young adults from Tecumseh, Mich. , the site of an ongoing cardiovascular epidemiological investigation. Our results suggest that the relation between MN phenotype and systolic blood pressure is significantly different and oppositely directed in men and women. Analysis of data available from previous examinations revealed that similar blood pressure differences related to MN phenotype had been present at least a decade earlier in both men and women. There also was a significant relation between systolic blood pressure and haptoglobin phenotype for the combined group of men and women. In addition to having high systolic blood pressure, men with the MM phenotype had significantly elevated red blood cell lithium-sodium countertransport activity. In studies of brother-brother pairs, we found evidence for significant genetic linkage between the MN locus and red blood cell lithium-sodium countertransport activity.