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.

Carvedilol Prevents Ovariectomy-Induced Myocardial Contractile Dysfunction in Female Rat

“…Carvedilol has high antioxidant activity compared to any other beta blocker [22]. In vitro and in vivo studies showed that carvedilol prevents lipid peroxidation in myocardial cell membranes initiated by ROS [39]. Our results also show that carvedilol decreased lipid peroxidation even though ovariectomy did not increase plasmatic MDA levels.…”

“…Clinical trials have shown that carvedilol improves heart function, morbidity, mortality rates of chronic heart failure patients and it has also been proven to be more effective than other beta blocker such as metoprolol [36]–[39]. Carvedilol has high antioxidant activity compared to any other beta blocker [22].…”

ß-Blocker Timolol Prevents Arrhythmogenic Ca2+ Release and Normalizes Ca2+ and Zn2+ Dyshomeostasis in Hyperglycemic Rat Heart

“…Furthermore, it was mentioned that non- selective β-blockers, aside from their β-blockage action [27], [28], [29], exert adrenoceptor-independent effects including scavenging of free radicals leading to controlled cellular redox status [30], [31]. We reported that chronic treatment with either timolol or propranolol demonstrates beneficial effects on heart function in male rats during increasing-age, whereas timolol, but not propranolol exerts similar beneficial effects in female rats [32], [33].…”

“…The diabetic heart is more susceptible to hypertensive or ischemic injury as a result of a number of pathological changes including cell death, increased oxidative stress, impaired Ca 2+ handling, and alterations in second messenger signaling pathways. As summarized in the introduction, some of the beneficial cardiovascular effects of β-ARs blockage have already been shown to be associated with their antioxidant properties by scavenging endogenous oxidants [30], [31]. Indeed, oxidative stress plays several critical roles in the development of diabetic cardiovascular complications, including myocardial hypertrophy.…”

Smad3 Inactivation and MiR-29b Upregulation Mediate the Effect of Carvedilol on Attenuating the Acute Myocardium Infarction-Induced Myocardial Fibrosis in Rat

“…The underlying mechanism whereby carvedilol attenuates AMI-induced cardiac remodeling seems to be multifactorial. Carvedilol has antioxidant activity [25], attenuates inflammatory mediators, and activates NF-kB [26]. Carvedilol treatment has been shown to delay oxidative-stress–induced apoptosis by improving Ca 2+ handling [27] and increasing the expression of anti-apoptosis proteins [28].…”