Effects of central and peripheral dopamine antagonism on aldosterone secretion: evidence for adrenal mechanism
Stern, N.; Eggena, P.; Chandler, W.; Tuck, M.L.
American Journal of Physiology 257(4 Pt 1): E588-E594
1989
ISSN/ISBN: 0002-9513 PMID: 2679132 Document Number: 328637
Both domperidone (DOMP) and metoclopramide (MCP) are D2 receptor antagonists, MCP being a central and peripheral dopamine antagonist, whereas DOMP is exclusively a peripheral antagonist. MCP, but not DOMP, has been shown to stimulate aldosterone production. To elucidate whether aldoseterone stimulation by dopamine antagonsim is centrally mediated, we injected DOMP (28 .mu.g/kg body wt) via a cannula into the third ventricle in Sprague-Dawley rats. Plasma aldosterone and renin concentration were measured before and 15 min after the injection. Centrally administered DOMP resulted in an increment in plasma aldosterone (23.8 .+-. 7.4 ng/dl) that was not significantly greater than that induced by vehicle alone (15.8 .+-. 4.5 ng/dl). This increase was inhibited by pretreatment with dexamethasone (100 .mu.g three times daily) and attenuated by captopril (1 mg/kg ip) but not by L-.beta.-3,4-dihydroxyphenyl-alanine (30 mg/kg), thus reflecting a stress effect. Similarly, central administration of MCP (21 .mu.g/kg) resulted in a significant rise in plasma aldosterone. This increase, however, was eliminated by pretreatment with dexamethesone and attenuated by captoril. Peripherally administered DOMP (280 .mu.g/kg) had not effect on plasma aldosterone. The effect of DOMP and MCP and aldosterone secretion by freshly obtained adrenal capsules was also tested. Angiotensin II and MCP, but not DOMP, induced a dose-dependent increase in aldosterone secretion, with a maximal increment (15.7 .+-. 5.8 ng .cntdot. mg capsular protein-1 .cntdot. 10 min-1; 50% increase) with MCP at 10-7 M (P < 0.01 compared with controls). Dopamine completely inhibited this MCP-induced rise in aldosterone release. Thus the dichotomous aldosterone response to MCP and DOMP cannot be explained by the inability of DOMP to cross the blood-brain barrier. These data support the concept of direct adrenal stimulation by MCP and and suggest the centrally administered DOMP or MCP does not enhance aldosterone release by a specific antidopaminergic mechanism but by a nonspecific stress effect.