Effects of NADPH oxidase inhibition on cardiac function and myocardial calcium regulatory proteins in rabbits with heart failure / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of NADPH oxidase inhibition on cardiac function and myocardial calcium regulatory proteins mRNA expressions in rabbits with heart failure (HF).</p><p><b>METHODS</b>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 c reduction. Sarcoplasmic reticulum Ca(2+)ATPase (SERCA2a), ryanodine receptor 2 (RyR2), phospholamban (PLB) and sodium-calcium exchanger (NCX) were determined by RT-PCR.</p><p><b>RESULTS</b>Rabbits with HF developed ventricular dilatation and cardiac dysfunction, as well as increase in myocardial NADPH oxidase activity, decreases in mRNA expression of SERCA2a, RyR2 and PLB, and increase in mRNA expression of NCX. Apocynin significantly reduced NADPH oxidase activity (P < 0.05), upregulated SERCA2a, RyR2 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/GAPDH1.28 +/- 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.</p><p><b>CONCLUSION</b>NADPH oxidase inhibition improves cardiac function possibly by preventing abnormal alterations in myocardial calcium regulatory proteins in failing heart.</p>