Blocking aldosterone action has been of clinical interest in the treatment of hypertension and related target organ damage. Although we have previously demonstrated aldosterone escape during long term administration of AT1 antagonist, pathological significance of aldosterone remains unknown. We investigated the effects of co-administration of spironolactone(SPRL) on the cardioprotective effects of AT1A in SHR-SP. Administration of AT1A alone resulted in a significant decrease in cardiac weight, cardiac transverse section area, cardiac fibrosis, and mRNA expression of BNP, type I and type III collagen, while cardiac ET-1 mRNA showed a significant increase. Co-administration of AT1A with SPRL resulted in a significant decrease in all the parameters including ET-1 mRNA expression. These results provide theoretical rationale for combination therapy of AT1A and SPRL in hypertension.
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