ABSTRACT
Beta-blockers have been used to treat ischemic heart disease, due to negative chronotropic and inotropic properties, thus inducing a decrease in myocardial consumption of oxygen and nutrients, allowing a better balance between nutritional needs and the supply provided by the coronary blood flow. Recent developments in cell biology allowed us to understand that not all beta-blockers are equal, as their intracellular mechanisms of action can be very different. This paper will focus on carvedilol, a non-selective beta-blocker with alfa-blocker properties, currently used to treat hypertension, heart failure and coronary artery disease. Effects of carvedilol on cardiac mitochondria, their relation to its antioxidant properties, and how these can improve cardiomyocyte resistance to aggression and cardiac function will be discussed. We will begin by depicting the effect of carvedilol on mitochondrial parameters, namely oxidative phosphorylation, calcium homeostasis and energy production. Then we will focus on the mitochondrial permeability transition (MPT) and how the antioxidant properties of carvedilol can be used to minimize oxidative stress, a powerful inducer of MPT. Carvedilol will also be highlighted as an enzyme modulator, focusing on its importance to prevent doxorubicin (DOX) cardiotoxicity. The mitochondrial-related mechanism of cardioprotection involving carvedilol will also be addressed, as we will discuss some clinical pieces of evidence showing the importance of mechanisms previously depicted. In conclusion, based upon its molecular mechanisms of action, carvedilol seems to be a unique beta-blocker. These unique characteristics can help us understand the positive impact of carvedilol on the prognosis of patients with heart disease.
