Relationship between cardiomyocyte cell death and cardiac function during hypertensive cardiac remodelling in Dahl rats.

The exact mechanisms responsible for the progression of heart failure remain unclear. We investigated the in vivo relationship between the incidence of apoptotic cell death and left ventricular function serially from the beginning of hypertension to decompensated heart failure in Dahl salt-sensitive rats. Dahl salt-resistant and Dahl salt-sensitive rats were fed on a high-salt diet from 6 weeks of age. Systolic blood pressure was recorded by the tail-cuff method every week. Cardiac function in vivo was evaluated by echocardiography and cardiac catheterization. Cardiomyocyte apoptosis was detected by the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) method. The gene expression of Bax, Bcl-2 and Bcl-xL was analysed by Northern blotting. The TUNEL method revealed that the incidence of cardiomyocyte apoptosis was significantly increased in the hearts of 18-week-old Dahl salt-sensitive rats (apoptotic index 1.3 +/- 0.1%). Northern blot analysis revealed that the Bcl-xL mRNA level increased gradually during the progression towards heart failure. In conclusion, these data suggest that cardiomyocyte apoptosis is a terminal event, and plays a role as an aggravating factor in the vicious cycle of heart failure.