Effects of central and peripheral dopamine antagonism on aldosterone secretion: evidence for adrenal mechanism.
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 aldosterone stimulation by dopamine antagonism is centrally mediated, we injected DOMP (28 micrograms/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 micrograms three times daily) and attenuated by captopril (1 mg/kg ip) but not by L-beta-3,4-dihydroxyphenylalanine (30 mg/kg), thus reflecting a stress effect. Similarly, central administration of MCP (21 micrograms/kg) resulted in a significant rise in plasma aldosterone. This increase, however, was eliminated by pretreatment with dexamethasone and attenuated by captopril. Peripherally administered DOMP (280 micrograms/kg) had no effect on plasma aldosterone. The effect of DOMP and MCP on 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.mg capsular protein-1.10 min-1; 50% increase) with MCP at 10(-7) M (P less than 0.01 compared with controls). Dopamine completely inhibited this MCP-induced rise in aldosterone release.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Medicine, Sepulveda Veterans Administration Medical Center, California.
Eggena
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Chandler
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Tuck
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ML
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism; D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D004294:Domperidone / Q000494:pharmacology*; D018492:Dopamine Antagonists; D007276:Injections, Intraventricular; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood
D018492:Dopamine Antagonists; D007980:Levodopa; D000450:Aldosterone; D004294:Domperidone; D003907:Dexamethasone; D002216:Captopril; D012083:Renin; D008787:Metoclopramide