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Role of B1 and AT2 Receptors in Cardiac Remodeling and Dysfunction in B2 Receptor Knockout Mice with Myocardial Infarction
Author(s) -
Xu Jiang,
Carretero Oscar A.,
Zhu Liping,
Shesely Edward G.,
Yang James J.,
Yang XiaoPing
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1037.3
Subject(s) - medicine , receptor , ejection fraction , myocardial infarction , endocrinology , angiotensin ii , blockade , ventricular remodeling , knockout mouse , kinin , bradykinin , heart failure
Activation of angiotensin II type 2 receptors (AT 2 R) contributes to cardioprotective effects of angiotensin receptor blockers, possibly via kinins acting on B 1 and B 2 receptors (B 1 R and B 2 R). Using B 2 R knockout mice (B 2 R−/− on B6;129SF2/J background, which have increased both B 1 R and AT 2 R expression), we tested the hypothesis that AT 2 R and B 1 R compensate for loss of B 2 R and that blockade of AT 2 R and/or B 1 R deteriorates cardiac remodeling and dysfunction in B 2 R−/− mice post myocardial infarction (MI). B 2 R−/− and wild‐type controls (WT) were subjected to sham MI or MI and treated with either vehicle, B 1 R antagonist (B 1 R‐ant, R892, 300 μg/kg/day), AT 2 R‐ant (PD123319, 20 mg/kg/day) or B 1 R‐ant + AT 2 R‐ant for 4 weeks. We found that 1) B 2 R−/− with sham MI had greater LV mass and myocyte cross‐sectional area (MCSA) than WT ( Figure 2) after MI, the increase in MCSA and interstitial collagen fraction (ICF) was greater in B 2 R−/−, but ejection fraction (EF) did not differ from WT; 3) B 1 R‐ant alone but not AT 2 R‐ant further increased MCSA and ICF and decreased EF in B 2 R−/−; and 4) blockade of both B 1 R and AT 2 R increased LV mass, diastolic dimension, MCSA and ICF and decreased EF further. Our results suggest that B 1 R and AT 2 R may play an important role in preventing deterioration of cardiac function and remodeling post‐ MI when B 2 R are absent. This work was supported by NIH grants HL28982, HL078951.