title: Benidipine reduces ischemia reperfusion-induced systemic oxidative stress through suppression of aldosterone production in mice.
abstract: Aldosterone is implicated in the pathogenesis of several cardiovascular diseases, including ischemia reperfusion (I/R) and myocardial infarction, and also causes oxidative stress and inflammation in cardiovascular systems. Benidipine, a long-acting T- and L-type calcium channel blocker, reduces infarct size following myocardial I/R in rabbits. Benidipine also inhibits the production of aldosterone in vitro. However, the precise mechanism of this phenomenon in vivo remains unknown. We therefore evaluated whether benedipine has a beneficial role through the regulation of oxidative stress in myocardial I/R. C57BL/6J mice were subjected to 30 min of left ascending coronary I/R. Benidipine was administered orally at 3 mg kg(-1) daily for 3 weeks without any changes in hemodynamic variables. Benidipine significantly reduced infarction size (13.4±2.5%) compared with controls (25.5±3.6%). Urinary 8-hydroxy-2' deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, increased significantly after I/R. I/R induced increases in 8-OHdG were significantly lower with benidipine. Local myocardial 8-OHdG was also elevated in I/R, but this augmentation was significantly suppressed with benidipine. The plasma aldosterone concentration (PAC) significantly increased 2 days after I/R and remained elevated at least 7 days after I/R. Treatment with benidipine significantly decreased I/R-induced elevation of the PAC. I/R-induced markers of fibrosis in hearts also reduced in benidipine. These results suggest that the administration of benidipine reduces myocardial infarct size as well as systemic oxidative stress after I/R. These phenomena are partially linked to reduced plasma aldosterone levels.
authors: Department of Disease Control and Homeostasis, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.
authors: Keisuke
authors: K
authors: Ohtani
authors: Soichiro
authors: S
authors: Usui
authors: Shuichi
authors: S
authors: Kaneko
authors: Shin-ichiro
authors: S
authors: Takashima
authors: Katsunori
authors: K
authors: Kitano
authors: Kanako
authors: K
authors: Yamamoto
authors: Masaki
authors: M
authors: Okajima
authors: Hiroshi
authors: H
authors: Furusho
authors: Masayuki
authors: M
authors: Takamura
mesh_terms: D000450:Aldosterone / Q000097:blood*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology*; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D000450:Aldosterone; C061004:benidipine