CHRONIC ADMINISTRATION OF ANGIOTENSIN-II RECEPTOR ANTAGONIST, TCV-116, IN CARDIOMYOPATHIC HAMSTERS

We examined whether specific blockade of the renin-angiotensin system is beneficial for the treatment of cardiac dysfunction in heart failure. The angiotensin II type-1 (AT(1)) receptor antagonist TCV-116 (10 mg.kg(-1).day(-1)) or its vehicle was given orally to UM-X 7.1 cardiomyopathic (CM) and normal Golden Syrian (GS) hamsters for 8 wk. Plasma and cardiac angiotensin II levels were significantly higher in CM than in GS hamsters. The CM heart showed a smaller response of left ventricular (LV) pressure and first derivative of maximal LV pressure (+dP/dt(max)) to the elevation of perfusion pressure (from 60 to 120 cmH(2)O) in Langendorff-perfused than in GS heart. Treatment with TCV-116 did not affect LV function in GS but significantly improved cardiac contractility in CM hamsters. These results suggest that the renin-angiotensin system plays an important role in the development of cardiac dysfunction due to cardiomyopathy. Blockade of this system by the AT(1) antagonist TCV-116 appears to be useful in the prevention of heart failure.