Study of metoprolol effect on connexin43 expression and distribution pattern in heart failure rats

Abstract

Objective To observe the effects of metoprolol (Meto) in different doses on myocardial connexin43 (Cx43) expression and distribution pattern in heart failure rats with chronic heart failure, so as to explore its cardiac protection mechanism. Methods One hundred Sprague-Dawley rats were randomly (random number) divided into 5 groups (n =20 in each group) : (1) sham group; (2) heart failure group (HF group) ; (3) low-dose metoprolol treated group [MetoA group, 1.25 mg/(kg·d)]; (4) medium-dose metoprolol treated group [MetoB group, 5 mg/(kg·d) ]; (5) large-dose metoprolol treated group [MetoC group, 20 mg/(kg·d)]. Rats of HF group and metoprolol treated group were subjected to abdominal aortic ligation, and different doses of metoprolol were given 4 weeks after ligation till 8 weeks. The rats were sacrificed 8 weeks after operation, and the myocardial Cx43 expression and distribution patterns were observed by using immunohistochemistry, and total Cx43 (T-Cx43) 、Phospho-Cx43 (P-Cx43) protein levels were detected by Western blotting. Results (1) In HF group, rat heart had obvious T-Cx43 disordered distribution with significant increase in Cx43 P-Cx43, T-Cx43 protein expression compared with Sham group; whereas medium-dose and low-dose Meto treatment did not significantly inhibit the T-Cx43 protein expression of HF rat heart, and large-dose Meto therapy could improve disordered T-Cx43 distribution and inhibit T-Cx43 protein expression of HF rat heart (P <0.01) . (2) Western blot showed P-Cx43 expression was significantly higher in the HF group than that in the sham group (P <0.01) , and in all metoprolol treated groups, P-Cx43 expressions were significantly decreased compared with the HF group (MetoA vs. HF, P <0.05; MetoB vs. HF, P <0.01; MetoC vs. HF, P <0.01) , and pairwise comparisons among the metoprolol treated groups also showed significant differences (P <0.01) . Conclusions Meto could exert a cardiac protective effect by inhibiting myocardial Cx43 phosphorylation and ameliorate its distribution disorder. Key words: Heart failure; Metoprolol; Gap junction channel; Connexin43