Nitric oxide is a preconditioning mimetic and cardioprotectant and is the basis of many available infarct-sparing strategies.

Ischemic preconditioning is a powerful infarct-sparing intervention. Intensive investigations have revealed many of the signaling steps used to elicit this protection. One of the steps involves activation of nitric oxide synthase (NOS) by phosphorylation, with the production of NO and subsequent activation of guanylyl cyclase, production of cGMP, activation of protein kinase G, opening of mitochondrial KATP channels, and generation of reactive oxygen species. The latter act as second messengers to activate critical kinase cascades that trigger entrance into the preconditioned state. Thus, NO exposure before ischemia can act as a powerful preconditioning mimetic. Elevating NO just prior to or at reperfusion can still be an effective cardioprotective strategy. Activation of NOS or production of NO can be done pharmacologically with exogenous agents to trigger this cascade. Many of these strategies are already available and safe.