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Chronic administration of angiotensin II receptor antagonist, TCV-116, in cardiomyopathic hamsters
F Nakamura1, M Nagano, R Kobayashi
1Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
Abstract:
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 (AT1) 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/dtmax) to the elevation of perfusion pressure (from 60 to 120 cmH2O) 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 AT1 antagonist TCV-116 appears to be useful in the prevention of heart failure.
Insights
Blocking the angiotensin II type-1 (AT1) receptor with TCV-116 improved cardiac contractility in cardiomyopathic hamsters. This suggests AT1 receptor antagonists may prevent heart failure by targeting the renin-angiotensin system.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- The renin-angiotensin system (RAS) is implicated in cardiac dysfunction.
- Understanding the role of specific RAS blockade in heart failure is crucial.
Purpose of the Study:
- To investigate the efficacy of angiotensin II type-1 (AT1) receptor blockade in treating cardiac dysfunction.
- To evaluate the therapeutic potential of TCV-116 in a hamster model of cardiomyopathy.
Main Methods:
- UM-X 7.1 cardiomyopathic (CM) and Golden Syrian (GS) hamsters were treated with TCV-116 (AT1 receptor antagonist) or vehicle for 8 weeks.
- Cardiac function was assessed using left ventricular (LV) pressure and +dP/dtmax measurements in Langendorff-perfused hearts.
- Plasma and cardiac angiotensin II levels were measured.
Main Results:
- CM hamsters exhibited higher plasma and cardiac angiotensin II levels compared to GS hamsters.
- CM hearts showed impaired LV pressure and +dP/dtmax responses to increased perfusion pressure.
- TCV-116 treatment significantly improved cardiac contractility in CM hamsters but did not affect LV function in GS hamsters.
Conclusions:
- The renin-angiotensin system plays a significant role in the development of cardiomyopathy-induced cardiac dysfunction.
- AT1 receptor antagonism with TCV-116 demonstrates potential therapeutic benefits for preventing heart failure.