title: Carvedilol inhibits mitochondrial oxygen consumption and superoxide production during calcium overload in isolated heart mitochondria.
abstract: BACKGROUND
  The COMET study suggested the better effect of carvedilol to metoprolol in treating heart failure. However, its underlying mechanisms of action remain unclear. As a result, evaluation of the distinct effects of both drugs on the mitochondrial function and reactive oxygen species (ROS) production during Ca(2+) overload was investigated.
  
  
  RESULTS
  The mitochondrial oxygen consumption (mVO(2)) and the mitochondrial ROS production in isolated rat heart mitochondria was measured. Ca(2+) overload from 10 to 100 micromol/L augmented mVO(2) was from 527+/-139 to 671 +/-138 nmol/mg (p<0.05), and this was then completely suppressed by carvedilol (1 micromol/L), but not by metoprolol (100 micromol/L). Ca(2+) overload augmented the ROS production upon complex I injury (9.7+/-1.2 to 11.4+/-1.4 nmol/mg, p<0.05). Carvedilol dose-dependently suppressed this ROS production, whereas metoprolol did not.
  
  
  CONCLUSIONS
  Carvedilol, but not metoprolol, was thus found to inhibit the calcium-dependent augmentation of mVO(2) and ROS production upon complex I injury. This new effect of carvedilol might partly explain the beneficial effect of carvedilol for the treatment of heart failure.
authors.affiliation: The Department of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kametani
authors.forename: Toshiro
authors.initials: T
authors.lastname: Miura
authors.forename: Nozomu
authors.initials: N
authors.lastname: Harada
authors.forename: Masaki
authors.initials: M
authors.lastname: Shibuya
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Tan
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fukagawa
authors.forename: Shuji
authors.initials: S
authors.lastname: Kawamura
authors.forename: Masunori
authors.initials: M
authors.lastname: Matsuzaki
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000188:drug therapy; D066298:In Vitro Techniques; D008297:Male; D008790:Metoprolol / Q000494:pharmacology / Q000627:therapeutic use; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects* / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D017382:Reactive Oxygen Species; D011943:Receptors, Adrenergic, beta; D000077261:Carvedilol; D013481:Superoxides; D008790:Metoprolol; D002118:Calcium