Combined Treatment With Valsartan and Spironolactone Prevents Cardiovascular Remodeling in Renovascular Hypertensive Rats

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Abstract
Treatment with an angiotensin blocker (ARB) and an aldosterone blocker has been shown to have beneficial effects on cardiac remodeling in several cardiac diseases. It is still not clear whether the combination of these drugs is more effective against cardiac remodeling than the use of either agent alone. We examined the effects of combined treatment with valsartan, an ARB, and spironolactone, an aldosterone blocker, on cardiac remodeling in the renovascular hypertensive (RHT) rat. The RHT rats were divided into 4 groups administered valsartan (3 mg/kg/day, ARB group), spironolactone (4 mg/kg/day, SPRL group), both drugs at these doses (combined group), or neither drug (untreated RHT group). After 5 weeks, systolic blood pressure was significantly reduced in the 3 treatment groups, however, there were no significant differences in the extent of blood pressure reduction among the 3 treatment groups. The heart weight/body weight ratio in each of the 3 treatment groups was significantly lower than that in the untreated RHT group. The degree of cardiac and perivascular fibrosis in the SPRL group and the combined group were significantly lower than that in the untreated RHT group. Myocyte remodeling in the ARB group and in the combined group was significantly smaller than that in the untreated RHT group. These results suggest that SPRL treatment prevents cardiac and perivascular fibrosis and ARB treatment suppresses the cellular hypertrophy of myocytes, and that, therefore, combined treatment with both drugs prevents cardiac remodeling by acting against both myocyte hypertrophy and cardiac fibrosis in RHT rats.