Effects of NADPH oxidase inhibition on cardiac function and myocardial calcium regulatory proteins in rabbits with heart failure
10.3760/cma.j.issn.0253-3758.2009.10.006
- VernacularTitle:抑制NADPH氧化酶对心力衰竭兔心肌钙调节蛋白的影响
- Author:
Yu LIU
1
;
He HUANG
;
Yan-Hong TANG
;
Hai-Tao LI
;
Xi WANG
;
Cong-Xin HUANG
Author Information
1. 武汉大学人民医院
- Keywords:
Heart failure;
congestive;
Oxidoreductases;
Calmodulin;
Ventricular function;
left
- From:
Chinese Journal of Cardiology
2009;37(10):883-886
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of NADPH oxidase inhibition on cardiac function and myocardial calcium regulatory proteins mRNA expressions in rabbits with heart failure (HF). Methods HF was induced by experimental aortic insufficiency and abdominal aortic constriction, HF animals were treated with oral apocynin (15 mg/d), a NADPH oxidase inhibitor or equal dose placebo. Eight weeks later, cardiac function was measured by echocardiography. Myocardial NADPH oxidase activity was evaluated by NADPH dependent superoxide production examined using superoxide dismutase-inhibitable cytochrome e reduction. Sarcoplasmic reticulum Ca~(2+) ATPase (SERCA2a), ryanodine receptor 2 (RyR2), phespholamban (PLB) and sedium-calcium exchanger (NCX) were determined by RT-PCR. Results Rabbits with HF developed ventricular dilatation and cardiac dysfunction, as well as increase in myocardial NADPH oxidaoe activity, decreases in mRNA expression of SERCA2a, RyPt2 and PLB, and increase in mRNA expression of NCX. Apocynin significandy reduced NADPH exidaae activity (P<0.05), upregulated SERCA2a, RyP,2 and PLB mRNA expressions (SERCA2a/GAPDH:0.63±0.11 vs. 0.34±0.08,RyR2/GAPDH:0.23±0.04 vs. 0.17±0.06,PLB/GAPDH:1.28±0. 13 vs. 0.95±0.09, P <0.05 ), downregulated NCX mRNA expression ( NCX/GAPDH :0.67±0.10 vs. 0.95±0.12, P<0.05 ), and improved cardiac function [ LVEF: (60.06±10.07) % vs. (38.87±3.31) %, LVFS: (30.12± 6.56)% vs. (17.40±2.45)%,P<0.05] in rabbits with HF. Conclusion NADPH oxidase inhibition improves cardiac function possibly by preventing abnormal alterations in myocardial calcium regulatory proteins in failing heart.
