Losartan reduces liver expression of plasminogen activator inhibitor-1 (PAI-1) in

ROSSELLI MS; BURGUEÑO A; CARABELLI J; SCHUMAN M; PIROLA CJ,; SOOKOIAN S

ATHEROSCLEROSIS

ELSEVIER IRELAND LTD

Año: 2009 vol. 206 p. 119 - 126

0021-9150

a b s t r a c t Objective: To evaluate 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) in a rat model of nonalcoholic fatty liver disease (NAFLD). Methods: Rats were given a high-fat diet (HFD) for 8 weeks and after this period were randomly divided into 3 groups. For 12 weeks along with the same access to HFD, one group (9 rats) received losartan and another group received telmisartan (10 rats), both at 10 mg/kg intraperitoneally (ip) every 24 h. The third group (8 rats) received saline ip along with the HFD. Finally, a control group (6 rats)was fed with standard chow diet for 20 weeks. Results: Fatty liver was reverted by both losartan and telmisartan. Both drugs had bene.cial effects on insulin resistance, reaching statistical signi.cance in telmisartan group. Expression of hepatic mRNA of PAI-1 showed a 42% decrease in losartan-treated rats incomparison with bothHFDgroup and telmisartantreated rats. To further evaluate this differential effect on PAI-1 expression, we explored the effect of the drugs on liver expression of TNF², PEPCK-C and PPAR², and no signi.cant differences were observed. Conclusion: These results indicate that AT1R blockers could be eligible drugs for reducing hepatic lipid accumulation in 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. © 2009 Elsevier Ireland Ltd. All rights reserved.