Inhibitory effect of efonidipine on aldosterone synthesis and secretion in human adrenocarcinoma (H295R) cells.

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Imagawa K, Okayama S, Takaoka M, Kawata H, Naya N, Nakajima T, Horii M, Uemura S, Saito Y

Inhibitory effect of efonidipine on aldosterone synthesis and secretion in human adrenocarcinoma (H295R) cells.

J Cardiovasc Pharmacol. 2006 Jan;47(1):133-8. doi: 10.1097/01.fjc.0000197539.12685.f5.

PubMed ID

16424797 [ View in PubMed

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Abstract

Targeting aldosterone synthesis and/or release represents a potentially useful approach to the prevention of cardiovascular disease. Aldosterone production is stimulated by angiotensin II (Ang II) or extracellular K+ and is mediated mainly by Ca2+ influx into adrenal glomerulosa cells through T-type calcium channels. We therefore examined the effects of efonidipine, a dual T-type/L-type Ca2+ channel blocker, on aldosterone secretion in the H295R human adrenocarcinoma cell line; 100 nmol/L Ang II and 10 mmol/L K+ respectively increased aldosterone secretion from H295R cells 12-fold and 9-fold over baseline. Efonidipine dose-dependently inhibited both Ang II- and K+-induced aldosterone secretion, and nifedipine, an L-type Ca2+ channel blocker, and mibefradil, a relatively selective T-type channel blocker, similarly inhibited Ang II- and K+-induced aldosterone secretion, but were much less potent than efonidipine. Efonidipine also lowered cortisol secretion most potently among these drugs. Notably, efonidipine and mibefradil also significantly suppressed Ang II- and K+-induced mRNA expression of 11-beta-hydroxylase and aldosterone synthase, which catalyze the final two steps in the aldosterone synthesis, whereas nifedipine reduced only K+-induced enzyme expression. These findings suggest that efonidipine acts via T-type Ca2+ channel blockade to significantly reduce aldosterone secretion, and that this effect is mediated, at least in part, by suppression of 11-beta-hydroxylase and aldosterone synthase expression.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Mibefradil	Cytochrome P450 11B1, mitochondrial	Protein	Humans	Unknown	Inhibitor	Details
Mibefradil	Cytochrome P450 11B2, mitochondrial	Protein	Humans	Unknown	Inhibitor	Details