期刊
HYPERTENSION
卷 45, 期 4, 页码 747-753出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.HYP.0000153322.04859.81
关键词
kinins; myocardial infarction; mice
资金
- NHLBI NIH HHS [R01 HL071806, HL-28982, P01 HL028982, HL-71806] Funding Source: Medline
Kinins exert cardioprotective effects via 2 G-protein-coupled receptors, B-1 and B-2. Using B-1 kinin receptor gene knockout mice (B-1(-/-)), we tested the hypotheses that the B-1 receptor plays an important role in preservation of cardiac function, whereas lack of B-1 may accelerate cardiac remodeling and dysfunction after myocardial infarction, and that B-2 receptors may compensate for lack of B-1, whereas blockade of B-2 receptors in B-1(-/-) mice may cause further deterioration of cardiac function and remodeling. Female B-1(-/-) mice and wild-type controls (C57BL/6J, B-1(+/+)) underwent sham surgery or myocardial infarction and were treated with either vehicle or B-2-antagonist ( icatibant, 500 mu g/kg per day, subcutaneous) for 8 weeks. We found that in sham myocardial infarction, B-1(-/-) mice had a larger left ventricular diastolic chamber dimension both initially and at 4 to 8 weeks compared with B-1(+/+). Left ventricular mass and myocyte size were also larger in B-1(-/-) with sham operation than in B-1(+/+), although cardiac function did not differ between strains. After myocardial infarction, cardiac remodeling and function were similar in both strains, although B-1(-/-) mice tended to have lower blood pressure. Blockade of B-2 receptors tended to worsen cardiac remodeling and dysfunction in B-1(-/-) but not in B-1(+/+). These results may suggest that B-2 receptors play an important role in compensating for lack of B-1 receptors in mice with myocardial infarction. Dual blockade of both B-1 and B-2 eliminates this compensation, leading to further deterioration of cardiac dysfunction and remodeling after myocardial infarction.
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