Effect of β-adrenergic receptor kinase inhibitor on post-myocardial infarction heart failure in rats

Objective: This study is to investigate the effect of β-adrenergic receptor kinase inhibitor (Adeno-βARKct) on heart failure (HF) rat model. Methods: Male SD rats weighted 250 g undertaken ligation of the left anterior de- scending branch of coronary artery to establish HF model. Survival rats were randomly divided into experimental treated group (EXP) and control treated group (CONT). Additionally, pseudo-operated rats were taken as sham-ligat- ed group (SHAM). Adeno-βARKct particles or Adeno empty vector was injected to the rats. Multiple indicators includ- ing left ventricular ejection fraction (LVEF), index of hemodynamics, plasma and myocardial tissue catecholamine, NT-ProBNP, mRNA levels of β1AR, β2AR and βARK1, and protein level of βARK1 were measured 4 weeks later. Results: Compared with rats in SHAM group, levels of LVEF, ±dp/dt max, and catecholamine in myocardial tissue were lower while plasma NT-ProBNP and plasma catecholamine were higher in rats of EXP and CONT. Additionally, β1AR and β2AR mRNA expressions were downregulated whereas βARK1 mRNA and βARK1 protein levels were up- regulated in EXP and CONT. Compared with CONT, the levels of LVEF, -dp/dt max, and catecholamine in myocardial tissue were higher, while plasma NT-ProBNP and plasma catecholamine were lower in EXP. β1AR and β2AR mRNA expressions were upregulated, whereas βARK1 mRNA expression and βARK1 protein levels were downregulated in EXP. Conclusion: In vivo delivery of Adeno-βARKct by caudal vein is feasible and can improve cardiac function in rats with HF after myocardial infarction.