Distinct effects of different β-adrenoceptor stimulation patterns on car-diac AMP-activated protein kinase activity
10.3969/j.issn.1000-4718.2016.12.009
- VernacularTitle:异丙基肾上腺素不同给药模式对小鼠心脏腺苷酸活化蛋白激酶活性的影响
- Author:
Han XIAO
;
Xiaowei MA
;
Yongnan FU
;
Youyi ZHANG
;
Zhizhen Lü
- Keywords:
β-Adrenoceptor;
AMP-activated protein kinase;
Isoproterenol
- From:
Chinese Journal of Pathophysiology
2016;32(12):2177-2183
- CountryChina
- Language:Chinese
-
Abstract:
[ ABSTRACT] AIM:To investigate the cardiac AMP-activated protein kinase ( AMPK) activity and the effects of AMPK activator on cardiac structure and function in the mice with different β-adrenoceptor (β-AR) stimulation patterns . METHODS:Male BALB/c mice were subcutaneously injected with AMPK activator ( AICAR, 250 mg· kg -1 · d-1 ) or saline, and infused with β-AR agonist isoproterenol (ISO, 5 mg· kg-1· d-1) for 14 d.The cardiac functions were evalu-ated by echocardiography or hemodynamic method , and the hearts were harvested after infusion cessation immediately or 3 d later.Phosphorylated AMPK ( p-AMPK) was measured by Western blot .RESULTS:Sustained ISO infusion increased p-AMPK level.AICAR did not further increase p-AMPK but attenuated ISO-induced increase in heart weight .Sustained ISO infusion increased cardiac systolic function as indicated by left ventricular fractional shortening ( FS) and maximum rate of pressure rise (+dp/dtmax).The cardiac systolic function was not further increased by AICAR .The cardiac diastolic func-tion as indicated by left ventricular end-diastolic pressure (LVEDP) was not different in each group .In contrast, cardiac p-AMPK level was similar between the control mice and the mice with sustained ISO infusion and ceased infusion for 3 d. In this model, AICAR improved the cardiac systolic and diastolic functions , which were impaired by ISO.Moreover, the increased pattern of p-AMPK level was similar with that of heart rate upon ISO stimulation .CONCLUSION: Sustained ISO infusion increases p-AMPK.After ISO infusion cessation for 3 d, p-AMPK is decreased to the basal level .β-AR-in-duced inotropic effects should be avoided to investigate the cardioprotective role of AMPK activation in the β-AR stimulation models.
