title: Azelnidipine inhibits aldosterone synthesis and secretion in human adrenocortical cell line NCI-H295R.
abstract: Blockade of a mineralocorticoid receptor is a clinically useful approach to the prevention of cardiovascular disease. The present study was designed to evaluate the effect of azelnidipine, a unique dihydropyridine Ca(2+) channel blocker, on aldosterone production in the human adrenocortical cell line NCI-H295R. Azelnidipine inhibited angiotensin II- and KCl-induced expression of steroid 11beta-hydroxylase, steroid 18-hydroxylase, and the alpha1H subunit of the T-type Ca(2+) channel, and suppressed steroid biosynthesis in H295R cells by the same amount as efonidipine. On the basis of these findings, azelnidipine appears to suppress steroid biosynthesis in H295R cells beyond the blockade of L-type calcium channels.
authors.affiliation: Department of Internal Medicine, Division of Diabetes and Endocrinology, Jikei University School of Medicine,Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Isaka
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ikeda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takada
authors.forename: Yuri
authors.initials: Y
authors.lastname: Inada
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Tojo
authors.forename: Naoko
authors.initials: N
authors.lastname: Tajima
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000378:metabolism; D018268:Adrenocortical Carcinoma / Q000378:metabolism; D000450:Aldosterone / Q000096:biosynthesis* / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D019405:Cytochrome P-450 CYP11B2 / Q000187:drug effects / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009596:Nitrophenols / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D013252:Steroid 11-beta-Hydroxylase / Q000187:drug effects / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D000804:Angiotensin II; C066425:efonidipine; D000450:Aldosterone; D001383:Azetidinecarboxylic Acid; D011189:Potassium Chloride; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; C061679:azelnidipine