Loss of bradykinin signaling does not accelerate the development of cardiac
dysfunction in type 1 diabetic akita mice.
Authors Wende AR, Soto J, Olsen CD, Pires KM, Schell JC, Larrieu-Lahargue F, Litwin SE,
Kakoki M, Takahashi N, Smithies O, Abel ED
Submitted By Oliver Smithies on 5/2/2011
Status Published
Journal Endocrinology
Year 2010
Date Published 8/1/2010
Volume : Pages 151 : 3536 - 3542
PubMed Reference 20501666
Abstract Bradykinin signaling has been proposed to play either protective or deleterious
roles in the development of cardiac dysfunction in response to various
pathological stimuli. To further define the role of bradykinin signaling in the
diabetic heart, we examined cardiac function in mice with genetic ablation of
both bradykinin B1 and B2 receptors (B1RB2R(-/-)) in the context of the Akita
model of insulin-deficient type 1 diabetes (Ins2(Akita/+)). In 5-month-old
diabetic and nondiabetic, wild-type and B1RB2R(-/-) mice, in vivo cardiac
contractile function was determined by left-ventricular (LV) catheterization and
echocardiography. Reactive oxygen species levels were measured by
2'-7'-dichlorofluorescein diacetate fluorescence. Mitochondrial function and ATP
synthesis were determined in saponin-permeabilized cardiac fibers. LV systolic
pressure and the peak rate of LV pressure rise and decline were decreased with
diabetes but did not deteriorate further with loss of bradykinin signaling. Wall
thinning and reduced ejection fractions in Akita mouse hearts were partially
attenuated by B1RB2R deficiency, although other parameters of LV function were
unaffected. Loss of bradykinin signaling did not increase fibrosis in
Ins2(Akita/+) diabetic mouse hearts. Mitochondrial dysfunction was not
exacerbated by B1RB2R deficiency, nor was there any additional increase in
tissue levels of reactive oxygen species. Thus, loss of bradykinin B2 receptor
signaling does not abrogate the previously reported beneficial effect of
inhibition of B1 receptor signaling. In conclusion, complete loss of bradykinin
expression does not worsen cardiac function or increase myocardial fibrosis in

Investigators with authorship
E. Dale AbelUniversity of Iowa
Oliver SmithiesUniversity of North Carolina
Nobuyuki TakahashiTohoku University