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Author Notes:

Correspondence to David J. Lefer, PhD, Department of Surgery, Division of Cardiothoracic Surgery, CT Surgery Research Laboratory, Emory University School of Medicine, 550 Peachtree St NE, Atlanta, GA 30308. dlefer@emory.edu



  • ischemia–reperfusion injury
  • arformoterol
  • β-adrenoreceptor
  • NO synthase
  • nitrite
  • nitrosothiol
  • Akt

Selective β2-Adrenoreceptor Stimulation Attenuates Myocardial Cell Death and Preserves Cardiac Function After Ischemia–Reperfusion Injury


Journal Title:

Arteriosclerosis, Thrombosis, and Vascular Biology


Volume 32, Number 8


, Pages 1865-1874

Type of Work:

Article | Post-print: After Peer Review


Objective β2-adrenoreceptor activation has been shown to protect cardiac myocytes from cell death. We hypothesized that acute β2-adrenoreceptor stimulation, using arformoterol (ARF), would attenuate myocardial ischemia/reperfusion (R) injury via NO synthase activation and cause a subsequent increase in NO bioavailability. Methods and Results Male C57BL/6J and endothelial NO synthase (eNOS) knockout mice were subjected to 45 minutes of myocardial ischemia and 24 hours of R. ARF or vehicle was administered 5 minutes before R. Serum troponin-I was measured, and infarct size per area-at-risk was evaluated at 24 hours of R. Echocardiography was performed at baseline and 2 weeks after R. Myocardial cAMP, protein kinase A, eNOS/Akt phosphorylation status, and NO metabolite levels were assayed. ARF (1 μg/kg) reduced infarct size per area-at-risk by 53.1% (P<0.001 versus vehicle) and significantly reduced troponin-I levels (P<0.001 versus vehicle). Ejection fraction was significantly preserved in ARF-treated hearts compared with vehicle hearts at 2 weeks of R. Serum cAMP and nuclear protein kinase A C-α increased 5 and 15 minutes after ARF injection, respectively (P<0.01). ARF increased Akt phosphorylation at Thr308 (P<0.001) and Ser473 (P<0.01), and eNOS phosphorylation at Ser1177 (P<0.01). ARF treatment increased heart nitrosothiol levels (P<0.001) at 15 min after injection. ARF failed to reduce infarct size in eNOS−/− mice. Conclusions Our results indicate that β2-adrenoreceptor stimulation activates cAMP, protein kinase A, Akt, and eNOS and augments NO bioavailability. Activation of this prosurvival signaling pathway attenuates myocardial cell death and preserves cardiac function after ischemia/reperfusion.

Copyright information:

© 2012 American Heart Association, Inc.

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