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

摘要

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 descending 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-ligated group (SHAM). Adeno-βARKct particles or Adeno empty vector was injected to the rats. Multiple indicators including 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 upregulated 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.