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Dilated and failing cardiomyopathy in bradykinin B2 receptor knockout mice

Emanueli, Costanza and Maestri, Roberta and Corradi, Domenico and Marchione, Roberta and Minasi, Alessandra and Tozzi, Maria Grazia and Salis, Maria Bonaria and Straino, Stefania and Capogrossi, Maurizio C. and Olivetti, Giorgio and Madeddu, Paolo (1999) Dilated and failing cardiomyopathy in bradykinin B2 receptor knockout mice. Circulation, Vol. 100 , p. 2359-2365. ISSN 0009-7322. eISSN 1524-4539. Article.

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DOI: 10.1161/01.CIR.100.23.2359

Abstract

Background - The activation of B2 receptors by kinins could exert cardioprotective effects in myocardial ischemia and heart failure.
Methods and Results — To test whether the absence of bradykinin B2 receptors may affect cardiac structure and function, we examined the developmental changes in blood pressure (BP), heart rate, and heart morphology of bradykinin B2 receptor gene knockout (B2−/−), heterozygous (B2+/−), and wild-type (B2+/+) mice. The BP of B2−/− 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 B2+/+, P<0.01). In B2+/− mice, BP elevation was delayed. At 40 days, the heart rate was higher (P<0.01) in B2−/− and B2+/− than in B2+/+ mice, whereas the left ventricular (LV) weight and chamber volume were similar among groups. Thereafter, the LV growth rate of B2−/− and B2+/− 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 B2+/+ mice. In B2−/− mice, hypertrophy was associated with a marked chamber dilatation (42% larger than that of B2+/+ mice), an elevation in LV end-diastolic pressure (25±3 versus 5±1 mm Hg in B2+/+ mice, P<0.01), and reparative fibrosis.
Conclusions — The disruption of the bradykinin B2 receptor leads to hypertension, LV remodeling, and functional impairment, implying that kinins are essential for the functional and structural preservation of the heart.

Item Type:Article
ID Code:10744
Status:Published
Refereed:Yes
Uncontrolled Keywords:Bradykinin, angiotensin, myocardium, hypertrophy, heart failure, blood pressure, genes
Subjects:Area 06 - Scienze mediche > MED/09 Medicina interna
Divisions:001 Università di Sassari > 03 Istituti > Clinica medica generale e terapia medica
002 Altri enti e centri di ricerca del Nord Sardegna > National laboratory of the national institute of biostructures and biosystems, Osilo
Publisher:Lippincott Williams & Wilkins
ISSN:0009-7322
eISSN:1524-4539
Copyright Holders:© 1999 by American Heart Association
Deposited On:03 Feb 2015 11:52

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