Chronic Co-Administration of Sepiapterin and L-Citrulline Ameliorates Diabetic Cardiomyopathy and Myocardial Ischemia/Reperfusion Injury in Obese Type 2 Diabetic Mice

Circulation. Heart Failure
Shelley L BaumgardtZhi-Dong Ge

Abstract

Diabetic heart disease is associated with tetrahydrobiopterin oxidation and high arginase activity, leading to endothelial nitric oxide synthase dysfunction. Sepiapterin (SEP) is a tetrahydrobiopterin precursor, and L-citrulline (L-Cit) is converted to endothelial nitric oxide synthase substrate, L-arginine. Whether SEP and L-Cit are effective at reducing diabetic heart disease is not known. The present study examined the effects of SEP and L-Cit on diabetic cardiomyopathy and ischemia/reperfusion injury in obese type 2 diabetic mice. Db/db and C57BLKS/J mice at 6 to 8 weeks of age received vehicle, SEP, or L-Cit orally alone or in combination for 8 weeks. Cardiac function was evaluated with echocardiography. Db/db mice displayed hyperglycemia, obesity, and normal blood pressure and cardiac function compared with C57BLKS/J mice at 6 to 8 weeks of age. After vehicle treatment for 8 weeks, db/db mice had reduced ejection fraction, mitral E/A ratio, endothelium-dependent relaxation of coronary arteries, tetrahydrobiopterin concentrations, ratio of endothelial nitric oxide synthase dimers/monomers, and nitric oxide levels compared with vehicle-treated C57BLKS/J mice. These detrimental effects of diabetes mellitus were abrogated by ...Continue Reading

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Citations

Jun 15, 2016·Scientific Reports·Hsiang-En WuZhi-Dong Ge
Jan 4, 2017·Journal of Diabetes·Yi Shi, Paul M Vanhoutte
Apr 12, 2019·International Heart Journal·Zhi-Dong GeZhengyuan Xia
Mar 28, 2018·The Journal of Pharmacology and Experimental Therapeutics·Christopher S RabenderRoss B Mikkelsen
Oct 18, 2019·Current Drug Delivery·Di ZhangYueze Liu
May 1, 2018·Journal of Diabetes Research·Francesco FaitaAnna Solini
Feb 26, 2020·Diabetes & Metabolism Journal·Johannes GollmerHeiko Bugger
Jul 12, 2017·F1000Research·Zeljko J Bosnjak, Zhi-Dong Ge
Mar 22, 2018·Frontiers in Cardiovascular Medicine·Keshav GopalJohn Reyes Ussher
Oct 22, 2018·BMC Cardiovascular Disorders·Tarun PantZhi-Dong Ge
Oct 23, 2018·Oxidative Medicine and Cellular Longevity·A C KellerJ E B Reusch
Apr 30, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hyoung Kyu Kim, Jin Han
Jul 3, 2021·International Journal of Molecular Sciences·Shuangyu LvHonggang Wang
Dec 12, 2021·Current Atherosclerosis Reports·Britt Burton-FreemanIndika Edirisinghe

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