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Alpha 1A‐Adrenergic Receptor Signaling Protects the Heart From Ischemic Injury Through an ERK‐Dependent Mechanism
Author(s) -
Rorabaugh Boyd R,
Handel Evelyn M,
Waterson Rachael E,
Talbot Jeffery N,
Perez Dianne M
Publication year - 2008
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/fasebj.22.1_supplement.1130.7
Subject(s) - mapk/erk pathway , ischemia , ischemic preconditioning , medicine , phosphorylation , perfusion , kinase , pharmacology , receptor , adrenergic receptor , reperfusion injury , signal transduction , extracellular , endocrinology , biology , microbiology and biotechnology
Brief periods of ischemia stimulate an endogenous mechanism in the heart that protects the myocardium from subsequent episodes of prolonged ischemia. This process, called “ischemic preconditioning”, is mimicked by signaling through α 1A ‐adrenergic receptors (ARs). Extracellular regulated kinases (ERK‐1 and ERK‐2) have been implicated in ischemic preconditioning. Therefore, we used mice expressing constitutively active mutant α 1A ‐adrenergic receptors (CAM α 1A ‐ARs) to determine whether α 1A ‐ARs protect the heart from ischemic injury through an ERK‐dependent mechanism. Western blots demonstrated that phosphorylation of ERK‐1 and ERK‐2 is significantly increased in CAM α 1A ‐AR hearts relative to nontransgenic hearts. Isolated hearts were perfused using the Langendorf method, and contractile function was monitored by an intraventricular balloon. Hearts isolated from CAM α 1A ‐AR or nontransgenic mice were subjected to 30 min ischemia and 1 hour reperfusion. Contractile function of CAM α 1A ‐AR hearts, but not nontransgenic hearts, completely recovered from 30 min ischemia. Perfusion with U0126 (MEK inhibitor) prior to the onset of ischemia blocked ERK phosphorylation and abolished the ability of CAM α 1A ‐AR hearts to recover from ischemia. These data support the conclusion that α 1A ‐ARs protect the heart from ischemic injury through an ERK‐dependent signaling pathway. (This study was supported by a Bower, Bennet, & Bennet Endowed Research Chair Award from Ohio Northern University).