Dilated and failing cardiomyopathy in bradykinin B-2 receptor knockout mice

Article

关键词: LEFT-VENTRICULAR HYPERTROPHY;    MYOCYTE CELL-DEATH;    ANGIOTENSIN-II;    ISCHEMIC CARDIOMYOPATHY;    CARDIAC-HYPERTROPHY;    HUMAN HEART;    IN-VITRO;    CARDIOVASCULAR PHENOTYPE;    HYPERTENSIVE RATS;    BLOOD-PRESSURE;   

DOI  :  10.1161/01.CIR.100.23.2359

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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