Dilated and failing cardiomyopathy in bradykinin B(2) receptor knockout mice.
BACKGROUND
The activation of B(2) receptors by kinins could exert cardioprotective effects in myocardial ischemia and heart failure.


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.
Emanueli
C
C
National Laboratory of the National Institute of Biostructures and Biosystems, Osilo, Italy.
Maestri
R
R
Corradi
D
D
Marchione
R
R
Minasi
A
A
Tozzi
M G
MG
Salis
M B
MB
Straino
S
S
Capogrossi
M C
MC
Olivetti
G
G
Madeddu
P
P
D000367:Age Factors; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure; D002311:Cardiomyopathy, Dilated / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood; D005355:Fibrosis; D015870:Gene Expression; D006339:Heart Rate; D006579:Heterozygote; D006720:Homozygote; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology*; D016234:Kallikrein-Kinin System / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics*; D012518:Sarcomeres / Q000473:pathology
D019332:Endothelin-1; D012333:RNA, Messenger; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D009320:Atrial Natriuretic Factor