Role of the B1 kinin receptor in the regulation of cardiac function and remodeling after myocardial infarction

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.