Cardiovascular System

Pflügers Archiv - European Journal of Physiology

, Volume 455, Issue 6, pp 971-978

Cyclooxygenase-2 mediates the delayed cardioprotection induced by hydrogen sulfide preconditioning in isolated rat cardiomyocytes

  • Li-Fang HuAffiliated withCardiovascular Biology Research Group, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
  • , Ting-Ting PanAffiliated withCardiovascular Biology Research Group, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
  • , Kay Li NeoAffiliated withCardiovascular Biology Research Group, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
  • , Qian Chen YongAffiliated withCardiovascular Biology Research Group, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
  • , Jin-Song BianAffiliated withCardiovascular Biology Research Group, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

We previously reported that hydrogen sulfide (H2S) preconditioning (SP) produces cardioprotection in isolated rat cardiomyocytes. The present study was designed to determine the involvement of cyclooxygenase-2 (COX-2) in the SP-induced delayed cardioprotection. Isolated cardiac myocytes were treated with NaHS (100 μM, a H2S donor) for 30 min and then cultured for 20 h followed by ischemia/reperfusion insults. SP significantly increased cell viability, percentage of rod-shaped cells, and myocyte contractility after 10 min of reperfusion. Given 30 min before and during lethal ischemia, two selective COX-2 inhibitors, NS-398 and celebrex, abrogated SP-induced cardioprotective effects. Moreover, SP upregulated the expression of COX-2 and increased PGE2 production in the cardiac myocytes. These effects were significantly attenuated by glibenclamide, an ATP-sensitive K+ channel (KATP) blocker, and chelerythrine, a selective protein kinase C (PKC) inhibitor, suggesting that activation of both KATP and PKC is required for the stimulation of COX-2. Additionally, NG-nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, failed to regulate COX-2 protein expression but inhibited SP-enhanced COX-2 activity and PGE2 production. In conclusion, we provided the first evidence that SP may produce delayed cardioprotection via KATP/PKC dependent induction of COX-2 expression and via nitric oxide-induced COX-2 activation.

Keywords

Cyclooxygenase-2 Hydrogen sulfide Ischemic preconditioning ATP-sensitive K+ channel Protein kinase C PGE2