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.
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