In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 293, No. 6 ( 2007-12), p. H3372-H3378
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.00997.2007
Language:
English
Publisher:
American Physiological Society
Publication Date:
2007
detail.hit.zdb_id:
1477308-9
SSG:
12
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