Dietary nitrite supplementation protects against myocardial ischemia-reperfusion injury.
Nitrite has emerged as an endogenous signaling molecule with potential therapeutic implications for cardiovascular disease. Steady-state levels of nitrite are derived in part from dietary sources; therefore, we investigated the effects of dietary nitrite and nitrate supplementation and deficiency on NO homeostasis and on the severity of myocardial ischemia-reperfusion (MI/R) injury. Mice fed a standard diet with supplementation of nitrite (50 mg/liter) in their drinking water for 7 days exhibited significantly higher plasma levels of nitrite, exhibited significantly higher myocardial levels of nitrite, nitroso, and nitrosyl-heme, and displayed a 48% reduction in infarct size (Inf) after MI/R. Supplemental nitrate (1 g/liter) in the drinking water for 7 days also increased blood and tissue NO products and significantly reduced Inf. A time course of ischemia-reperfusion revealed that nitrite was consumed during the ischemic phase, with an increase in nitroso/nitrosyl products in the heart. Mice fed a diet deficient in nitrite and nitrate for 7 days exhibited significantly diminished plasma and heart levels of nitrite and NO metabolites and a 59% increase in Inf after MI/R. Supplementation of nitrite in the drinking water for 7 days reversed the effects of nitrite deficiency. These data demonstrate the significant influence of dietary nitrite and nitrate intake on the maintenance of steady-state tissue nitrite/nitroso levels and illustrate the consequences of nitrite deficiency on the pathophysiology of MI/R injury. Therefore, nitrite and nitrate may serve as essential nutrients for optimal cardiovascular health and may provide a treatment modality for cardiovascular disease.
Bryan
Nathan S
NS
Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA.
Calvert
John W
JW
Elrod
John W
JW
Gundewar
Susheel
S
Ji
Sang Yong
SY
Lefer
David J
DJ
D000284:Administration, Oral; D000818:Animals; D019587:Dietary Supplements; D004353:Drug Evaluation, Preclinical; D006418:Heme / Q000031:analogs & derivatives / Q000032:analysis; D051379:Mice; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000502:physiology; D009573:Nitrites / Q000008:administration & dosage / Q000627:therapeutic use*; D015538:Nitrosation / Q000187:drug effects; D009603:Nitroso Compounds / Q000032:analysis
D009566:Nitrates; D009573:Nitrites; D009603:Nitroso Compounds; D009569:Nitric Oxide; D006418:Heme; C027417:nitrosylprotoheme