Interaction between bradykinin subtype 2 and angiotensin II type 2 receptors during post-MI left ventricular remodeling.
Angiotensin II type 2 receptor (AT(2)R) overexpression (AT(2)TG) attenuates left ventricular remodeling in a mouse model of anterior myocardial infarction (MI). We hypothesized that the beneficial effects of cardiac AT(2)TG are mediated via the bradykinin subtype 2 receptor (B(2)R). Fourteen transgenic mice overexpressing the AT(2)R (AT(2)TG mice), 10 mice with a B(2)R deletion (B(2)KO mice), 13 AT(2)TG mice with B(2)R deletion (AT(2)TG/B(2)KO mice), and 11 wild-type (WT) mice were studied. All mice were on a C57BL/6 background. Mice were studied by cardiac magnetic resonance imaging at baseline and days 1, 7, and 28 after MI induced by 1 h of occlusion of the left anterior descending artery followed by reperfusion. Short-axis images from apex to base were used to compare ventricular volumes and ejection fraction (EF). At baseline, end-diastolic volume index (EDVI) and end-systolic volume index (ESVI) were lower and EF higher in AT(2)TG mice compared with the other three strains. Infarct size was similar between groups. No differences were observed in global remodeling parameters at day 28 between AT(2)TG and AT(2)TG/B(2)KO mice; however, EDVI and ESVI were lower and EF higher in both transgenic groups than in WT or B(2)KO mice. Both strains lacking B(2)R demonstrated increased collagen content and less hypertrophy in adjacent noninfarcted regions at day 28. Attenuation of postinfarct remodeling by overexpression of AT(2)R is not directly mediated via a B(2)R pathway. However, B(2)R does appear to have a role in the smaller cavity size and hyperdynamic function observed at baseline in AT(2)TG mice and in limiting collagen deposition during postinfarct remodeling.
Isbell
David C
DC
Cardiovascular Division, Department of Medicine, University of Virginia Health System, 1215 Lee Street, Charlottesville, VA 22908, USA.
Voros
Szilard
S
Yang
Zequan
Z
DiMaria
Joseph M
JM
Berr
Stuart S
SS
French
Brent A
BA
Epstein
Frederick H
FH
Bishop
Sanford P
SP
Wang
Hongkun
H
Roy
Rene J
RJ
Kemp
Brandon A
BA
Matsubara
Hiroaki
H
Carey
Robert M
RM
Kramer
Christopher M
CM
D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D048429:Cell Size; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D006339:Heart Rate; D019028:Magnetic Resonance Imaging, Cine; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013318:Stroke Volume; D013997:Time Factors; D017725:Ventricular Pressure; D020257:Ventricular Remodeling
D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D003094:Collagen