Targeting Adrenergic Receptors in Metabolic Therapies for Heart Failure: A Review

When the heart fails, it loses its ability to generate enough energy, resulting in an energy- starved condition with diminished functioning. Studies have identified numerous changes in the metabolic pathways in the failing heart that cause a reduction in the oxidation of either glucose and/or fatty acid substrates. This reduced oxidation arises from defects in mitochondrial functions and/or oxidative phosphorylation, which leads to reduced energy output required to mediate cardiac contraction. Inhibitors of fatty acid oxidation and antioxidants that target the mitochondria have been shown in early-stage clinical investigations to enhance heart function during failure by enhancing compensatory glucose oxidation. Adrenergic receptors ( 1 and ) are a key sympathetic nervous system regulator that controls cardiac function. -AR blockers are an established treatment for heart failure and 1A-AR agonists have potential therapeutic benefit. In addition to controlling inotropy and chronotropy, 1- and -adrenergic receptors in the heart also control metabolic activities that are responsible for numerous cardiac benefits. Our objective in this review is to highlight recent studies that describe how adrenergic receptor-mediated metabolic pathways may be able to restore cardiac energetics to non-failing levels that may offer promising therapeutic strategies.