Exploring the role and inter-relationship among nitric oxide, opioids, and KATP channels in the signaling pathway underlying remote ischemic preconditioning induced cardioprotection in rats

Document Type: Original Article


Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, 147002 India


Objective(s): This study explored the inter-relationship among nitric oxide, opioids, and KATP channels in the signaling pathway underlying remote ischemic preconditioning (RIPC) conferred cardioprotection.
Materials and Methods: Blood pressure cuff was placed around the hind limb of the animal and RIPC was performed by 4 cycles of inflation (5 min) followed by deflation (5 min). An ex vivo Langendorff’s isolated rat heart model was used to induce ischemia (of 30 min duration)-reperfusion (of 120 min duration) injury.
Results: RIPC significantly decreased ischemia-reperfusion associated injury assessed by decrease in myocardial infarct, LDH and CK release, improvement in postischemic left ventricular function, LVDP, dp/dtmax, and dp/dtmin. Pretreatment with L-NAME and naloxone abolished RIPC-induced cardioprotection. Moreover, preconditioning with sodium nitroprusside (SNP) and morphine produced a cardioprotective effect in a similar manner to RIPC. L-NAME, but not naloxone, attenuated RIPC and SNP preconditioning-induced increase in serum nitrite levels. Morphine preconditioning did not increase the NO levels, probably suggesting that opioids may be the downstream mediators of NO. Furthermore, glibenclamide and naloxone blocked cardioprotection conferred by morphine and SNP, respectively.
Conclusion: It may be proposed that the actions of NO, opioids, and KATP channels are interlinked. It is possible to suggest that RIPC may induce the release of NO from endothelium, which may trigger the synthesis of endogenous opioids, which in turn may activate heart localized KATP channels to induce cardioprotection.


Main Subjects

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