Premium
The role of β‐Adrenergic Receptor Signaling in Cardioprotection
Author(s) -
Tong Haiyan,
Bernstein Daniel,
Murphy Elizabeth,
Steenbergen Charles
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-3067fje
Subject(s) - cardioprotection , ischemia , medicine , chemistry , ischemic preconditioning , adrenergic receptor , cardiology , receptor , pharmacology
This study examines the role of the β2‐adrenergic receptor (β2‐AR) in cardioprotection. The β2‐AR couples to Gs and Gi proteins. Gs activates PKA, which phosphorylates the receptor and switches β2‐AR coupling from Gs to Gi. Prior to 20 min of global ischemia, mouse hearts were either perfused for 30 min without treatment (control), treated with 10 nmol/L of isoproterenol (ISO) for 5 min followed by 5 min washout, or preconditioned with 4 cycles of 5 min ischemia and 5 min reflow (PC). Recovery of left ventricular developed pressure (LVDP) and infarct size were measured. Intermittent ISO treatment improved post‐ischemic recovery of LVDP (58.5±4.8% vs. 22.0±6.3% in control) and reduced infarct size (31.0±2.4% vs. 53.0±4.6% in control). The Gi inhibitor pertussis toxin blocked the ISO‐induced improvement in postischemic LVDP and infarct size. To test the role of β2‐AR in PC, we studied mice lacking β2‐AR (β2‐AR−/−) and found that PC had no effect on postischemic LVDP or infarct size in β2‐AR−/−. To test whether PKA is required for the PC and ISO‐induced protection, hearts were treated with the PKA inhibitors PKI and H‐89. We found that PKI and H‐89 blocked the PC‐ and ISO‐induced improvement in postischemic LVDP and infarct size. These data show an important role for β2‐AR in cardioprotection and support the novel hypothesis that preconditioning involves switching of β2‐AR coupling from Gs to Gi.