Role of the B 1 Kinin Receptor in the Regulation of Cardiac Function and Remodeling After Myocardial Infarction

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Abstract
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 μg/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.