Expression of bradykinin receptors in the left ventricles of rats with pressure overload hypertrophy and heart failure.

OBJECTIVES

Bradykinin exerts cardioprotective effects through bradykinin type-2 receptors (BK-2Rs). After acute myocardial infarction in rat, the heart adapts by increasing its number of BK-2Rs. However, in human chronic end-stage heart failure, the number of BK-2Rs is significantly decreased. Thus, the presence of a cardioprotective BK-2R signaling system may be critical in the prevention of pressure overload-induced heart failure.

DESIGN

To explain differences in myocardial BK-2R expression during cardiac overload, we studied: (1). spontaneously hypertensive rats (SHRs) of different ages, and (2). normotensive Sprague-Dawley rats subjected to aortic banding or angiotensin II infusion.

METHODS AND RESULTS

The mRNA levels of BK-2Rs were found to be significantly (P < 0.05) increased in the aging (12 and 20-month-old) SHRs (2.9- and 3-fold, respectively). Similarly, in the Sprague-Dawley rats, the expression of BK-2Rs was increased at 12 h (1.8-fold, P < 0.05) and at 3 days (3.1-fold, P < 0.05) after aortic banding, and at 2 weeks (2.2-fold) after angiotensin II infusion. In the 12-month-old SHRs, with compensated left ventricular hypertrophy (no fibrosis or left ventricular dysfunction), the amount of BK-2Rs was also significantly increased (1.8-fold, P < 0.05). However, in the 20-month-old SHRs, with a dramatic increase in fibrosis and development of diastolic dysfunction and heart failure, the amount of BK-2Rs were significantly decreased (63%, P < 0.05) specifically in the cardiac endothelial cells.

CONCLUSIONS

The present results show that, during pressure overload and compensated left ventricular hypertrophy, the expression of BK-2Rs is increased. However, ongoing pressure overload leads to a loss of BK-2Rs with a dramatic increase in left ventricular fibrosis followed by diastolic dysfunction and heart failure.