Distinctive effects of carvedilol in the non-infarct zone: remodelling of the ligated rat heart linked to oxidative stress.
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.
Zhuang
X F
XF
Department of Cardiology, Peking University People's Hospital, Beijing, China.
Yin
C Q
CQ
Wang
H Y
HY
Sun
Ning Ling
NL
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*
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