[Effects of NADPH oxidase inhibition on cardiac function and myocardial calcium regulatory proteins in rabbits with heart failure].
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 c reduction. Sarcoplasmic reticulum Ca(2+)ATPase (SERCA2a), ryanodine receptor 2 (RyR2), phospholamban (PLB) and sodium-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 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/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.


CONCLUSIONS
NADPH oxidase inhibition improves cardiac function possibly by preventing abnormal alterations in myocardial calcium regulatory proteins in failing heart.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Yu
Y
Liu
He
H
Huang
Yan-hong
YH
Tang
Hai-tao
HT
Li
Xi
X
Wang
Cong-xin
CX
Huang
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002147:Calmodulin / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D016277:Ventricular Function, Left; D000099211:Phospholamban
D000098:Acetophenones; D002118:Calcium; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D004791:Enzyme Inhibitors; D019255:NADPH Oxidases; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger; D000099211:Phospholamban; C110374:sodium-calcium exchanger 1; C056165:acetovanillone