title: Distinctive effects of carvedilol in the non-infarct zone: remodelling of the ligated rat heart linked to oxidative stress.
abstract: In this study, an experimental rat ligated heart model was used to observe the effect of treatment with carvedilol, metoprolol and metoprolol plus a highly selective alpha(1)-adrenergic blocking agent, bunazosin, after acute myocardial infarction (MI). Compared with an untreated MI group, all drug-treated groups demonstrated attenuation of inflammatory mediators, activation of nuclear factor-kappaB (NF-kappaB), and increased levels of mRNA and active protein for the collagenases matrix metallopeptidase (MMP)-8 and MMP-13 in the non-infarct zone of the ventricle, as well as inhibition of the increase of left ventricular end-diastolic pressure. Supplementation of metoprolol with bunazosin did not add greatly to the effects of metoprolol alone. Of the three drug treatments, carvedilol showed a uniquely potent antioxidant activity that may strengthen its capacity to inhibit oxidative stress, the release of inflammatory mediators and activation of NF-kappaB. This study may help provide a mechanistic explanation for the greater benefits shown by carvedilol compared with metoprolol in treating heart failure.
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China.
authors.forename: X F
authors.initials: XF
authors.lastname: Zhuang
authors.forename: C Q
authors.initials: CQ
authors.lastname: Yin
authors.forename: H Y
authors.initials: HY
authors.lastname: Wang
authors.forename: Ning Ling
authors.initials: NL
authors.lastname: Sun
mesh_terms: D000208:Acute Disease; D000818:Animals; D000975:Antioxidants; D015153:Blotting, Western; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D004338:Drug Combinations; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006321:Heart / Q000187:drug effects*; D018836:Inflammation Mediators / Q000378:metabolism; D008026:Ligation; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000235:genetics / Q000378:metabolism; D008790:Metoprolol / Q000494:pharmacology; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D011412:Propanolamines / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D002227:Carbazoles; D004338:Drug Combinations; D018836:Inflammation Mediators; D016328:NF-kappa B; D011412:Propanolamines; D011799:Quinazolines; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014665:Vasodilator Agents; D000077261:Carvedilol; C018176:bunazosin; D053509:Matrix Metalloproteinase 13; D020784:Matrix Metalloproteinase 8; D008790:Metoprolol