Interaction between bradykinin subtype 2 and angiotensin II type 2 receptors during post-MI left ventricular remodeling

Abstract

Angiotensin II type 2 receptor (AT2R) overexpression (AT2TG) attenuates left ventricular remodeling in a mouse model of anterior myocardial infarction (MI). We hypothesized that the beneficial effects of cardiac AT2TG are mediated via the bradykinin subtype 2 receptor (B2R). Fourteen transgenic mice overexpressing the AT2R (AT2TG mice), 10 mice with a B2R deletion (B2KO mice), 13 AT2TG mice with B2R deletion (AT2TG/B2KO 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 AT2TG 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 AT2TG and AT2TG/B2KO mice; however, EDVI and ESVI were lower and EF higher in both transgenic groups than in WT or B2KO mice. Both strains lacking B2R demonstrated increased collagen content and less hypertrophy in adjacent noninfarcted regions at day 28. Attenuation of postinfarct remodeling by overexpression of AT2R is not directly mediated via a B2R pathway. However, B2R does appear to have a role in the smaller cavity size and hyperdynamic function observed at baseline in AT2TG mice and in limiting collagen deposition during postinfarct remodeling.