title: Rapid induction of aldosterone synthesis in cultured neonatal rat cardiomyocytes under high glucose conditions.
abstract: In addition to classical adrenal cortical biosynthetic pathway, there is increasing evidence that aldosterone is produced in extra-adrenal tissues. Although we previously reported aldosterone production in the heart, the concept of cardiac aldosterone synthesis remains controversial. This is partly due to lack of established experimental models representing aldosterone synthase (CYP11B2) expression in robustly reproducible fashion. We herein investigated suitable conditions in neonatal rat cardiomyocytes (NRCMs) culture system producing CYP11B2 with considerable efficacy. NRCMs were cultured with various glucose doses for 2-24 hours. CYP11B2 mRNA expression and aldosterone concentrations secreted from NRCMs were determined using real-time PCR and enzyme immunoassay, respectively. We found that suitable conditions for CYP11B2 induction included four-hour incubation with high glucose conditions. Under these particular conditions, CYP11B2 expression, in accordance with aldosterone secretion, was significantly increased compared to those observed in the cells cultured under standard-glucose condition. Angiotensin II receptor blocker partially inhibited this CYP11B2 induction, suggesting that there is local renin-angiotensin-aldosterone system activation under high glucose conditions. The suitable conditions for CYP11B2 induction in NRCMs culture system are now clarified: high-glucose conditions with relatively brief period of culture promote CYP11B2 expression in cardiomyocytes. The current system will help to accelerate further progress in research on cardiac tissue aldosterone synthesis.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo 105-8461, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Fujisaki
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Nagoshi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Taro
authors.initials: T
authors.lastname: Date
authors.forename: Michihiro
authors.initials: M
authors.lastname: Yoshimura
mesh_terms: D000450:Aldosterone / Q000096:biosynthesis*; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D012333:RNA, Messenger; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D005947:Glucose; D019808:Losartan