To investigate the role of beta3-adrenergic receptor (β3-AR) in the myocardium of chronic heart failure (CHF) and its association with phosphatidylinositol 3 kinase (PI3K)-protein kinase B (Akt).

Totally 16 Wistar rats were divided into a control group and a doxorubicin group, with eight rats in each group. Rats in the doxorubicin group were intraperitoneally injected with doxorubicin twice a week (1 mg/kg each time), and rats the control group were injected with the same amount of isosmotic NaCl solution (1 mL/kg each time). Kept for three weeks after eight weeks of injection, all rats were weighed and killed directly. The plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and nitric oxide of rats in the two groups were detected by enzyme-linked immunosorbent assay, and the myocardial conditions were observed by hematoxylin-eosin (HE) staining. The messenger RNA (mRNA) levels of β3-AR, PI3K and Akt in the ventricular muscle were determined by real-time fluorescence quantitative PCR, and the protein levels of β3-AR, PI3K, phospho-Akt (p-Akt) and Akt were detected by Western-blotting.

At the end of the experiment, the body mass of rats in the doxorubicin group was significantly lower than that in the control group [(275 ± 6) g vs. (353 ± 5) g, t = 9.571, P < 0.001], while the plasma NT-proBNP level was significantly higher [(2 158 ± 69) ng/L vs. (1 071 ± 59) ng/L, t = 11.969, P < 0.001]. HE staining showed that the myocardial structure of rats in the control group was clear, the muscle fibers were neatly arranged and tightly connected, and there was no cell edema and necrosis. The myocardial cells of rats in the doxorubicin group were not striped, the myocardial fibers were disordered, and there was cell edema, gap widening, inflammatory cell infiltration and a small amount of patchy necrosis. The mRNA and protein levels of myocardial β3-AR (t = 2.418, 6.965; both P < 0.05), PI3K (t = 3.704, 4.926; both P < 0.05) and the protein levels of p-Akt (t = 7.210, P < 0.001) in the doxorubicin group were significantly higher than those in the control group. Pearson correlation analysis showed that the mRNA and protein levels of myocardial β3-AR (r = 0.749, 0.803; both P < 0.05) were positively correlated to PI3K, and the protein level of β3-AR was positively correlated to p-Akt protein (r = 0.748, P = 0.001).

In the rats with CHF, the levels of β3-AR are significantly elevated and closely related to PI3K and p-Akt, which may affect doxorubicin-induced CHF through the PI3K-Akt signaling pathway.