Differential role of kinin B1 and B2 receptors in ischemia-induced apoptosis and ventricular remodeling.
We investigated the role of kinin receptors in cardiac remodeling after ischemia/reperfusion (I/R). Bradykinin injection improved cardiac contractility, diastolic function, reduced infarct size and prevented left ventricular thinning after I/R, whereas des-Arg(9)-BK injection had no protective effects. Bradykinin, but not des-Arg(9)-BK, reduced cardiomyocyte apoptosis and increased Akt and GSK-3beta phosphorylation. Furthermore, myocardial infarct size was similar between wild type and B2 knockout mice after I/R, but significantly reduced in kinin B1 receptor knockout mice. These results indicate that the kinin B2 receptor, but not the B1 receptor, protects against I/R-induced cardiac dysfunction by inhibiting apoptosis and limiting ventricular remodeling.
Yin
Hang
H
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425-2211, USA.
Chao
Julie
J
Bader
Michael
M
Chao
Lee
L
D000818:Animals; D017209:Apoptosis; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006352:Heart Ventricles / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009203:Myocardial Infarction / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1 / Q000502:physiology*; D043782:Receptor, Bradykinin B2 / Q000502:physiology*; D015427:Reperfusion Injury / Q000503:physiopathology*; D020257:Ventricular Remodeling
D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; D051058:Oncogene Protein v-akt; D038362:Glycogen Synthase Kinase 3