Abstract
OBJECTIVES: We investigated the effect of chronic administration of an angiotensin II type-1 receptor antagonist in the development of heart failure due to volume overload in rats. METHODS: Aortocaval fistula (AVF), a model of volume overloaded heart failure, was induced in rats by our newly developed technique using a simple and rapid 18-gauge needle multipuncture. After 3 weeks of oral administration of an angiotensin II receptor antagonist TCV-116, 1 mg/kg per day, we evaluateeift ventricular dilatation. We also compared the effect of TCV-116 with that of an angiotensin-converting enzyme inhibitor delapril, 1 g/L in drinking water. RESULTS: AVF heart failure produced by our technique exhibited significant increases in the left ventricular end-diastolic pressure (LVEDP)(12±1 vs 4±1 mmHg, p<0.05), right atrial pressure (RAP)(5.0±0.6 vs 1.0±0.4 mmHg, p<0.05), right ventricular systolic pressure (RVSP)(58±6 vs 33±1 mmHg, p<0.05), left ventricular weight (LVW)(3.00±0.13 vs 2.09±0.04 g/kg BW, p<0.05), right ventricular weight (RVW)(0.93±0.05 vs 0.59±0.01 g/kg BW, p<0.05), and left ventricular end-diastolic volume index (LVEDVI) (2.55±0.14 vs 0.80±0.12 ml/kg BW, p<0.05) as compared with these values in shamoperated rats. There were no differences in shunt ratio between untreated and TCV-116- and delapril-treated AVF groups. TCV-116 improved these hemodynamics, as did delapril (TCV-116 vs delapril: LVEDP 8±1 vs 8±1, RAP: 3.8±0.6 vs 2.3±1.4, RASP: 50±2 vs 46±3, LVW: 2.53±0.11 vs 2.52±0.15, RVW: 0.80±0.04 vs 0.77±0.06, LVEDVI: 1.67±0.15 vs 1.70±0.17). CONCLUSION: These results suggest that AVF rats with volume overload produced by a new multipuncture method exhibit both right- and left-side heart failure. Angiotensin II type-1 receptor antagonist as well as angiotensin converting enzyme inhibitor attenuate the development of this type of heart failure in rats.
