Opposing Effects of β ₁ - and β ₂ -Adrenergic Receptors on Cardiac Myocyte Apoptosis

Abstract

In ARVMs, stimulation of beta(1)-ARs increases apoptosis via a cAMP-dependent mechanism, whereas stimulation of beta(2)-ARs inhibits apoptosis via a G(i)-coupled pathway. These findings have implications for the pathophysiology and treatment of myocardial failure.

β-adrenoceptor blocker treatment and the cardiac β-adrenoceptor-G-protein(s)-adenylyl cyclase system in chronic heart failure

“…On the other hand, it could be protective to the heart because it could augment antiapoptotic effects. Recent studies had shown that, at least in rat cardiomyocytes, cardiac β-AR stimulation does not only evoke chrono-and inotropic effects but can also affect apoptosis with β-1 AR (via the G s -protein) inducing proapoptotic effects and β-2 AR (via the G i -protein) inducing antiapoptotic effects (Communal et al 1999;Xiao et al 2004). If this would occur also in the human heart, the increase in G i -protein in CHF should promote antiapoptosis.…”

The Effects of Nebivolol on Apoptosis in a Rat Infarct Model

“…22,23 Although the mechanism has not been fully explained, in vitro studies showed that noradrenaline (via 1 receptors) activates caspases, that are basic apoptotic enzymes. 24,25 Nebivolol is a 3 rd generation -blocker that has also a NO regulating effect. Although the effects of NO on apoptosis have been evaluated in many studies, the results of these studies were controversial.…”

“…22,23,38,39 It is known that noradrenaline induce apoptosis via -adrenergic receptors. 24 It is also known that although -1 adrenergic receptors stimulate apoptosis, -2 receptors thought to not only stimulate but also inhibits apoptosis. 24 However, prevention of apoptosis by nebivolol might possibly be via -blockage activity, our findings indicate that NO regulating effect of nebivolol might also be important in this effect.…”

Cardiac gene therapy in large animals: bridge from bench to bedside

“…Whereas b1-AR stimulation induces myocyte apoptotic signaling, b2-AR stimulation protects against apoptosis signaling. 69 With the support of improved cardiac performance in b2-AR-overexpressed rats and rabbits, the effect of b2-AR overexpression was evaluated in piglets. Adenoviral b2-AR delivery to neonatal piglets during cardiopulmonary bypass was associated with improved post-operative cardiac function.…”