Exendin-4, glucagon-like peptide-1 receptor agonist, enhances isoflurane-induced preconditioning against myocardial infarction via caveolin-3 expression.
OBJECTIVE
To investigate the cardioprotective effects of isoflurane and exendin-4 against myocardial ischemia/reperfusion injury and the signaling pathways through which these effects are mediated.


METHODS
For infarct size measurements, anesthetized mice were subjected to 30 min of coronary artery occlusion followed by 2 h of reperfusion. Wild-type or caveolin-3 knockout mice received isoflurane, exendin-4, or isoflurane with exendin-4 before ischemia index determination. Caveolin-3 expression in the heart was measured by immunoblotting.


RESULTS
Myocardial infarct size was smaller in the isoflurane- [1.0 minimum alveolar concentration (MAC)] or exendin-4- (30 ng/kg i.v.) treated groups than the controls. Infarct size was not affected by isoflurane at 0.5 MAC or 3 ng/kg i.v. exendin-4, but the combination of these treatments reduced infarct size. Pharmacological preconditioning (isoflurane at 1.0 MAC, 30 ng/kg i.v. exendin-4, or isoflurane at 0.5 MAC with 3 ng/kg i.v. exendin-4) increased caveolin-3 protein expression in the heart after infarct induction. The cardioprotective effects of isoflurane, exendin-4, and isoflurane with exendin-4 were abolished in caveolin-3 knockout mice.


CONCLUSIONS
The combination of isoflurane and exendin-4 reduced infarct size, but it was not more effective than either agent alone, and the cardioprotective effects of these agents are mediated by caveolin-3 expression.
Department of Anesthesiology, Department of Nutrition, the University of Tokushima, Tokushima, Japan. tsutsumi@tokushima-u.ac.jp.
E
E
Hamaguchi
K
K
Tanaka
R
R
Tsutsumi
Y
Y
Sakai
K
K
Fukuta
A
A
Kasai
Y M
YM
Tsutsumi
D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D000818:Animals; D051244:Caveolin 3 / Q000096:biosynthesis*; D004359:Drug Therapy, Combination; D000077270:Exenatide; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007530:Isoflurane / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D010455:Peptides / Q000008:administration & dosage*; D014688:Venoms / Q000008:administration & dosage*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
D018685:Anesthetics, Inhalation; D051244:Caveolin 3; D010455:Peptides; D014688:Venoms; D000077270:Exenatide; D007530:Isoflurane; D000097789:Glucagon-Like Peptide-1 Receptor Agonists