ANGIOTENSIN-II TYPE-1 RECEPTOR ANTAGONIST AS WELL AS ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR ATTENUATES THE DEVELOPMENT OF HEART-FAILURE IN AORTOCAVAL FISTULA RATS

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 evaluated the hemodynamics, heart weight, and degree of left 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 sham-operated 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.