Dual blockade of angiotensin- II and aldosterone suppresses the progression of a non-diabetic rat model of steatohepatitis.

Aim Both angiotensin- II ( AT-II) and aldosterone ( Ald) play pivotal roles in the pathogenesis of diseases in several organs including the liver. We previously reported that suppression of AT-II and Ald with angiotensin-converting enzyme inhibitor ( ACE- I) and selective Ald blocker ( SAB), respectively, attenuated the rat liver fibrogenesis and hepatocarcinogenesis. The aim of our current study was to elucidate the combined effects of ACE- I and SAB in the progression of a non-diabetic rat model of steatohepatitis, and the possible mechanisms involved. Methods In the choline-deficient L-amino acid-defined ( CDAA) diet-induced model, the effects of ACE- I and SAB on liver fibrosis development and hepatocarcinogenesis were elucidated, especially in conjunction with neovascularization. Results Treatment with both ACE- I and SAB suppressed the development of liver fibrosis and glutathione- S-transferase placental form ( GST- P) positive pre-neoplastic lesions. The combined treatment with both agents exerted more inhibitory effects as compared with either a single agent along with suppression of the activated hepatic stellate cells ( Ac- HSC) and neovascularization, both of which play important roles in these processes. Our in vitro study showed that AT-II type 1 receptor blocker ( ARB) and SAB inhibited Ac- HSC proliferation and in vitro angiogenesis along with suppression of the in vivo studies. Conclusion Dual blockade of AT-II and Ald suppresses the progression of a non-diabetic rat model of steatohepatitis. Because both agents are widely and safely used in clinical practice, this combination therapy could be an effective new strategy against steatohepatitis in the future. [ABSTRACT FROM AUTHOR]