Inhibition of NADPH oxidase alleviates experimental diabetes-induced myocardial contractile dysfunction

Diabetes, Obesity and MetabolismVolume 13, Issue 5 p. 465-473 Inhibition of NADPH oxidase alleviates experimental diabetes-induced myocardial contractile dysfunction Correction(s) for this article Corrigendum Volume 24Issue 10Diabetes, Obesity and Metabolism pages: 2066-2067 First Published online: August 8, 2022 N. D. Roe, N. D. Roe Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY, USASearch for more papers by this authorD. P. Thomas, D. P. Thomas Division of Kinesiology & Health, College of Health Sciences, University of Wyoming, Laramie, WY, USASearch for more papers by this authorJ. Ren, Corresponding Author J. Ren Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY, USADr. Jun Ren, Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, 1000 E. University Ave, Laramie, WY 82071, USA.E-mail: [email protected]Search for more papers by this author N. D. Roe, N. D. Roe Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY, USASearch for more papers by this authorD. P. Thomas, D. P. Thomas Division of Kinesiology & Health, College of Health Sciences, University of Wyoming, Laramie, WY, USASearch for more papers by this authorJ. Ren, Corresponding Author J. Ren Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY, USADr. Jun Ren, Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, 1000 E. University Ave, Laramie, WY 82071, USA.E-mail: [email protected]Search for more papers by this author First published: 27 January 2011 https://doi.org/10.1111/j.1463-1326.2011.01369.xCitations: 49Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Aim: O2− production is implicated in cardiac dysfunction for a number of diseases including diabetes. Activation of the O2−-producing enzyme NADPH oxidase is seen in diabetes, although its role in diabetic cardiomyopathy is unclear. This study was designed to evaluate the effect of NADPH oxidase inhibition on cardiac function in diabetes. Methods: Experimental diabetes was induced in adult C57 mice using streptozotocin (STZ, 150 mg/kg, i.p.) prior to the administration of the NADPH oxidase inhibitor apocynin (4 mg/kg/day) for 2 weeks. Left ventricular (LV) and myocyte contractile functions were evaluated using echocardiography and edge-detection, respectively. Results: STZ elicited hyperglycaemia and reduced body weight gain, which was unaffected by apocynin. STZ significantly reduced fractional shortening, LV wall thickness, peak shortening, maximal velocity and duration of shortening or relengthening, the effects of which – with the exception of wall thickness – were significantly attenuated or ablated by apocynin. Western blot analysis revealed that the effects of comparable Akt phosphorylation, reduced AMPK phosphorylation, downregulation of sarco(endo)plasmic reticulum Ca2+-ATPase and lessened phosphorylation of phospholamban in diabetic myocardium were unaffected by apocynin. Both apocynin and the nitric oxide synthase (NOS) inhibitor l-arginine methyl ester (L-NAME) inhibited elevated O2− production in diabetes without any additive effect between the two, indicating the presence of endothelial nitric oxide synthase (eNOS) uncoupling. However, neither diabetes nor apocynin altered the expression of heat shock protein 90 and eNOS phosphorylation (Ser1177). In addition, apocynin mitigated elevated levels of nitrotyrosine and nitric oxide in diabetes. Conclusion: Taken together, these data indicate the beneficial role of NADPH oxidase inhibition in diabetes-induced myocardial contractile dysfunction. Citing Literature Volume13, Issue5May 2011Pages 465-473 RelatedInformation