Losartan reduces liver expression of plasminogen activator inhibitor-1 (PAI-1) in a rat model of fatty liver disease.

MARIA SOLEDAD ROSSELLI; BURGUEÑO A,; CARABELLI, JULIETA; SCHUMAN, MARIANO; PIROLA CJ; SOOKOIAN S

San Francisco, USA.

Congreso; Annual meetting of the American Association for the Study of Liver Diseases; 2008

AASLD

This study evaluated the effect of Losartan-an angiotensin II type 1 receptor (AT1R) antagonist- and Telmisartan-an AT1R blocker with insulin-sensitizing properties-, on the hepatic expression of plasminogen activator inhibitor-1 (PAI-1) and tumor necrosis factor-alpha (TNFa) in a rat model of nonalcoholic fatty liver disease (NAFLD). Additionally, we explored the pharmacological effect on hepatic steatosis. Methods: Rats were given a high-fat diet (HFD) for 8 weeks and after this period were randomly divided in 3 groups. For 12 weeks along with the same access to HFD, one group (9 rats) received losartan and another group was given telmisartan (10 rats), both at 10 mg/kg intraperitoneally (ip) every 24 hours. The third group (8 rats) received saline ip along with the HFD. A control group was included (6 rats) that were fed with standard chow diet for 20 weeks. Results: Fatty liver was reverted by both losartan and telmisartan; however, only telmisartan improved insulin resistance. Expression of hepatic mRNA of PAI-1 showed a 42 % decrease in losartan-treated group in comparison with both HFD group and telmisartan-treated rats. Neither in losartan nor in telmisartan-treated groups the expression of hepatic TNFa was significantly different in comparison with the HFD group. In conclusions, these results indicate that AT1R blockers could be drugs of first choice for the treatment of patients with NAFLD. However, only 12 weeks of losartan treatment strongly reduced hepatic PAI-1 gene expression. These differences could provide even more effective options for preventing fatty liver disease and its cardiovascular complications.