Furthermore, the activation of b2-AR in the diseased heart can increase the risk for arrhythmias. Accordingly, the resulting restoration of the b-AR balance by Flecainide acetate exercise may provide a therapy to prevent cardiac dysfunction. In contrast to b1- and b2-AR, b3-AR modulates a negative inotropic effect through inhibitory G-protein CGS 19755 coupled NOS/NO signaling. After MI, b3-AR is activated by high concentrations of norepinephrine and is described as a counter-mechanism during sympathetic overstimulation. Recently, b3-AR has been shown to play a protective role in the development of MI. The stimulation of b3-AR blunts cardiac contractile responses and improves LV function in the failing heart. Additionally, specific b3-AR agonists can protect the heart from cardiac hypertrophy through generating NO and reducing ROS. In this study, the data showed that compared with the MI group, exercise significantly increased the protein expression of b3-AR in the LV, implying that b3-AR may play a role in the beneficial effects of exercise. Although it is still unclear how exercise protects against MI, our data suggest that b3-AR is involved in this process. The upregulation of the b3-AR may trigger many cytoprotective signaling cascades, which ultimately contribute to the cardioprotection. In this study, our attention was focused on NOS2 and NOS1 in the heart. Previous studies suggested that NOS2 was solely responsible for b3-AR-induced NO production. However, new research indicates that NOS1 also plays a key role in b3-AR signaling. The importance of NOS1 to cardiac calcium cycling and contractility has been revealed in recent studies. In the present study, NOS1 protein expression in the LV increased after MI. And exercise increased the expression of NOS1 and the activation of NOS2 without altering total NOS2, suggesting that exercise upregulates b3-AR expression, making b3-AR a possible source for NOS2 and NOS1 activation. Recent studies have shown that activation of NOS2 and NOS1 is essential for b3-AR-induced cardioprotection, and the beneficial effects of b3-AR stimulation were lost in NOS2 and NOS1 knockout mice. Importantly, NOS2 and NOS1 are indispensable for the cardiac adaptive effects of exercise. New data suggests that the beneficial effects of exercise are mediated by increased NOS1 signaling, which leads to increased cardiac calcium cycling, followed by enhanced contraction and accelerated relaxation. Furthermore, exercise failed to produce any beneficial adaptations in NOS2 and NOS1 knockout mice. This suggests that the beneficial effects of the b3-AR stimulation after exercise may be associated with the activation of NOS2 and NOS1. Additionally, in this study, both b2-AR/b1-AR and b3-AR/b1-AR ratios were closely correlated with hemodynamics, this implied that the normalization of b-AR balance by exercise may be associated with improvement of cardiac function.