Nitric Oxide and Adenosine Triphosphate-Sensitive Potassium Channels

SummaryMyocardial protection by ischemic preconditioning is effective in experimental studies, and ischemic preconditioning can also prevent cellular damage in many tissues and organs. This has encouraged investigators in various fields to study ischemic preconditioning intensively. In search of the essential cardioprotective factors, they have begun to clarify the major events during brief periods of ischemia. Ca2+ overload, free radicals, catecholamines, cytokines, and hormones have been proposed as candidate causes of ischemic damage but have also been identified as triggers for ischemic preconditioningderived cardioprotection. Ischemic preconditioning leads to the activation of intracellular messengers, including nitric oxide (NO) and KATP channels, and other enzymes to produce a cardioprotective effect. These two agents have essentially different properties. However, they appear to use the analogous pathways to reduce the severity of both myocardial infarction and myocardial dysfunction such as stunning, hibernating myocardium, and remodeling. Because preconditioning ischemia must precede lethal ischemia for these effects to occur, the underlying mechanisms such as NO and the opening of KATP channel should be effectively applied to strategies for protection after ischemic insults. Here, we summarize previous and current investigations related to the interaction of NO and KATp channels, especially in cardioprotection including controversial issues, and discuss the future directions of investigation, including some successfully Proceeding clinical trials.