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This Article Full Text Full Text (PDF) All Versions of this Article: 289/5/H2251    most recent 00341.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Guo, Y. Articles by Bolli, R. Search for Related Content PubMed PubMed Citation Articles by Guo, Y. Articles by Bolli, R.

Late preconditioning induced by NO donors, adenosine A₁ receptor agonists, and ₁-opioid receptor agonists is mediated by iNOS

Institute of Molecular Cardiology, University of Louisville, Louisville, Kentucky

Submitted 5 April 2005 ; accepted in final form 6 July 2005

Although ischemia-induced late preconditioning (PC) is known to be mediated by inducible nitric oxide (NO) synthase (iNOS), the role of this enzyme in pharmacologically induced late PC remains unclear. We tested whether targeted disruption of the iNOS gene abrogates late PC elicited by three structurally different NO donors [diethylenetriamine/NO (DETA/NO), nitroglycerin (NTG), and S-nitroso-N-acetyl-penicillamine (SNAP)], an adenosine A₁ receptor agonist [2-chloro-N⁶-cyclopentyladenosine (CCPA)], and a ₁-opioid receptor agonist (TAN-670). The mice were subjected to a 30-min coronary occlusion followed by 24 h of reperfusion. In iNOS knockout (iNOS^–/–) mice, infarct size was similar to wild-type (WT) controls, indicating that iNOS does not modulate infarct size in the absence of PC. Pretreatment of WT mice with DETA/NO, NTG, SNAP, TAN-670, or CCPA 24 h before coronary occlusion markedly reduced infarct size. In iNOS^–/– mice, however, the late PC effect elicited by DETA/NO, NTG, SNAP, TAN-670, and CCPA was completely abrogated. Furthermore, in WT mice pretreated with TAN-670 or CCPA, the selective iNOS inhibitor 1400W also abolished the delayed PC properties of these drugs; 1400W had no effect in WT mice. These data demonstrate that iNOS plays an obligatory role in NO donor-induced, adenosine A₁ receptor agonist-induced, and ₁-opioid receptor agonist-induced late PC, underscoring the critical role of this enzyme as a common mediator of cardiac adaptations to stress.

nitric oxide; inducible nitric oxide synthase; myocardial ischemia; reperfusion injury

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