Magnesium modulates ouabain action on angiotensin II-induced aldosterone synthesis in vitro.
Ouabain can block the action of angiotensin II (AII on aldosterone secretion in both rat and human adrenal tissue although its action is much more potent on human zona glomerulosa cells (ZG). Since magnesium can antagonize digitalis action in vivo, we have examined the interaction of both agents on aldosterone secretion in both rat and human adrenal cells. Ouabain itself at high concentration (10(-5) M) in Mg++ buffer blocks AII action on aldosterone secretion on rat ZG cells and at 1000-fold lower concentrations inhibits AII-action in human cells as previously reported by us. When buffer Mg++ is higher (4mM) than normal (0.7 mM) in cultured human adrenal cells it decreases both basal aldosterone secretion (8.6 +/- 0.4 vs. 6.8 +/- 0.2, p < 0.001) and AII action on aldosterone (13.9 +/- 0.6 vs. 9.7 +/- 0.7 ng/10(6) cells/h, p < 0.01). High Mg++ buffer had this effect at both 10(-8) and 10(-7) M concentrations of ouabain (control 8.6 +/- 0.4, AII [10(-9) M] 13.9 +/- 0.7, AII + Ouabain [5 x 10(-8) M] 10.9 +/- 0.6, AII + ouabain [10(-7) M] 7.8 +/- 0.3 ng/10(6) cells/h, both p < 0.01 vs. AII). In contrast, a low Mg++ buffer stimulated both basal (6.9 +/- 0.2 vs. 8.3 +/- 0.4 ng/10(6) cells/h, p < 0.01) and AII stimulation of aldosterone secretion (8.4 +/- 0.2 vs. 9.8 +/- 0.4 ng/10(6) cells/h, p < 0.01). When ouabain was added to low Mg++ buffer there was further inhibition of AII induced aldosterone secretion than with normal Mg++ buffer. However, the effect of ACTH on aldosterone was not altered by changes in Mg++. We conclude that ouabain actions and the effect of angiotensin II on aldosterone is inhibited by an increased level of Mg++ while low levels of Mg++ are stimulatory to both basal and AII action on aldosterone.
Antonipillai
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I
Department of Medicine, University of Southern California School of Medicine, Los Angeles, USA.
Hong
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Horton
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R
D000450:Aldosterone / Q000096:biosynthesis* / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002021:Buffers; D004347:Drug Interactions; D006801:Humans; D008274:Magnesium / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015384:Zona Glomerulosa / Q000187:drug effects* / Q000378:metabolism*
D002021:Buffers; D000804:Angiotensin II; D000450:Aldosterone; D010042:Ouabain; D008274:Magnesium