Dilated and failing cardiomyopathy in bradykinin B2 receptor knockout mice

Background-The activation of B-2 receptors by kinins could exert cardioprotective effects in myocardial ischemia and heart failure. Methods and Results-To test whether the absence of bradykinin B-2 receptors may affect cardiac structure and function, we examined the developmental changes in blood pressure (BP), heart rate, and heart morphology of bradykinin B-2 receptor gene knockout (B-2(-/-)), heterozygous (B-2(+/-)), and wild-type (B-2(+/+)) mice. The BP of B-2(-/-) mice, which was still normal at 50 days of age, gradually increased, reaching a plateau at 6 months (136 +/- 3 versus 109 +/- 1 mm Hg in B-2(+/+) P < 0.01). In B-2(+/-) mice, BP elevation was delayed. At 40 days, the heart rate was higher (P < 0.01) in B-2(-/-) and B-2(+/-) than in B-2(+/+) mice, whereas the left ventricular (LV) weight and chamber volume were similar among groups. Thereafter, the LV growth rate of B-2(-/-) and B-2(+/-) mice was accelerated, leading at 360 days to a LV weight-to-body weight ratio that was 9% and 17% higher, respectively, than that of B-2(+/+) mice, In B-2(-/-) mice, hypertrophy was associated with a marked chamber dilatation (42% larger than that of B-2(+/+) mice), an elevation in LV end-diastolic pressure (25 +/- 3 versus 5 +/- 1 mm Hg in B-2(+/+) mice, P < 0.01), and reparative fibrosis, Conclusions-The disruption of the bradykinin B-2 receptor leads to hypertension, LV remodeling and functional impairment, implying that kinins are essential for the functional and structural preservation of the heart.