The role of dopamine in nonmodulating hypertension.
Dopamine may exert a tonic inhibitory effect on aldosterone secretion and enhance renal sodium excretion. Nonmodulating hypertension in part is characterized by decreased aldosterone secretion in response to angiotensin II (AII) as well as a decreased natriuretic response to a saline load. This study assesses whether an abnormally increased dopaminergic inhibition of aldosterone secretion underlies the adrenal defect in nonmodulating hypertension and whether abnormalities of renal dopamine formation contribute to sodium retention. We measured the plasma dopamine concentration in 39 patients with nonmodulating hypertension and in 32 patients with normal modulation on a 10-meq sodium intake. Dopamine levels were significantly higher (P less than 0.05) in nonmodulators. The aldosterone response to AII (3 ng/kg.min) was assessed before and during administration of the dopamine antagonist metoclopramide in 13 patients. Metoclopramide did not change the adrenal response to AII in either hypertensive subgroup. In 12 normal subjects mean urinary dopamine levels were higher in a sodium-replete state (200-mmol intake) than in a low sodium state (10-mmol intake; 1.68 +/- 0.28 vs. 0.92 +/- 0.22 mumol/day; P less than 0.01) as expected. Modulators demonstrated this same effect, while nonmodulators did not [modulators, 3.66 +/- 0.82 and 1.37 +/- 0.14 mumol/day; nonmodulators, 1.33 +/- 0.28 and 1.68 +/- 0.90 mumol/day; P less than 0.02]. The sodium-retaining tendency of nonmodulators may reflect, at least in part, reduced intrarenal dopamine production in the sodium-replete state, but the adrenal defect in aldosterone release in nonmodulators is not mediated by excess dopaminergic inhibition of aldosterone secretion.
Gordon
M S
MS
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Steunkel
C A
CA
Conlin
P R
PR
Hollenberg
N K
NK
Williams
G H
GH
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D000804:Angiotensin II; D004039:Diet, Sodium-Restricted; D004298:Dopamine / Q000096:biosynthesis* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007262:Infusions, Intravenous; D008297:Male; D008787:Metoclopramide / Q000008:administration & dosage; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D012964:Sodium / Q000378:metabolism
D000804:Angiotensin II; D000450:Aldosterone; D012964:Sodium; D008787:Metoclopramide; D004298:Dopamine