Heart failure, oxidative stress, and ion channel modulation.
The balance of reactive oxygen species (ROS) and nitric oxide, the cell redox state, appears to be important in the mechanisms of heart failure. This balance has significant impact on calcium-handling proteins, affecting excitation-contraction coupling. Both ROS and nitric oxide appear to be elevated in heart failure and are accompanied by significant impairments in the number and function of calcium-handling proteins. These proteins contain sulfhydryl groups or disulfide linkages involving cysteine residues, making them susceptible to the action of oxidizing-reducing agents and nitrosylation, thereby altering their properties. Initial increases in nitric oxide may be an adaptive response to myocardial dysfunction, elevated cytokines, and increases in ROS, while a further increase in nitric oxide and overwhelming ROS can be damaging. Abundant nitric oxide and ROS can cause formation of peroxynitrite, a strong oxidant, or nitric oxide can activate alternate pathways aiding the ROS, causing impaired calcium handling contributing to contractile dysfunction.
Choudhary
Gaurav
G
Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA, USA.
Dudley
Samuel C
SC
D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium