Critical role for nitric oxide signaling in cardiac and neuronal ischemic preconditioning and tolerance

Krishnadas Nandagopal, Ted M. Dawson, Valina L. Dawson

Research output: Contribution to journalReview articlepeer-review


Preconditioning to ischemic tolerance is a phenomenon in which brief episodes of a subtoxic insult induce a robust protection against the deleterious effects of subsequent, prolonged, lethal ischemia. The subtoxic stimuli that constitute the preconditioning event are quite diverse, ranging from brief ischemic episodes, spreading depression or potassium depolarization, chemical inhibition of oxidative phosphorylation, exposure to excitotoxins and cytokines. The beneficial effects of preconditioning were first demonstrated in the heart; it is now clear that preconditioning can induce ischemic tolerance in a variety of organ systems including brain, heart, liver, small intestine, skeletal muscle, kidney, and lung. There are two temporally and mechanistically distinct types of protection afforded by preconditioning stimuli, acute and delayed preconditioning. The signaling cascades that initiate the acute and delayed preconditioning responses may have similar biochemical components. However, the protective effects of acute preconditioning are protein synthesis-independent, mediated by post-translational protein modifications, and are short-lived. The effects of delayed preconditioning require new protein synthesis and are sustained for days to weeks. Elucidation of the molecular mechanisms that are involved in preconditioning and ischemic tolerance and identification of drugs that mimic this protective response have the potential to improve the prognosis of patients at risk for ischemic injury. This article focuses on recent findings on the effects of ischemic preconditioning in the cardiac and nervous systems and discusses potential targets for a successful therapeutic approach to limit ischemia-reperfusion injury.

Original languageEnglish (US)
Pages (from-to)474-478
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
StatePublished - 2001

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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