Journal
ATHEROSCLEROSIS
Volume 206, Issue 1, Pages 119-126Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2009.01.026
Keywords
Nonalcoholic fatty liver disease; Plasminogen activator inhibitor-1; Angiotensin II receptor blacker; Angiotensin II type 1 receptor; Losartan; Telmisartan
Funding
- Universidad de Buenos Aires [UBACYT M055]
- Agencia Nacional de Promocion Cientifica y Tecnologica [PICT 05-25920, PICT 06124]
- Consejo Nacional de Investigaciones Cientificas y Tecnicas [PIP 5195]
- Fundacion Alfredo Lanari, and Consejo de Investigacion de la Ciudad Autonoma de Bs
- Consejo Nacional de Investigaciones Cientificas
- Consejo de lnvestigacion de la Ciudad de Buenos Aires
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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 beneficial effects on insulin resistance, reaching statistical significance in telmisartan group. Expression of hepatic mRNA of PAI-1 showed a 42% decrease in losartan-treated rats in comparison with both HFD group and telmisartan-treated rats. To further evaluate this differential effect on PAI-1 expression, we explored the effect of the drugs on liver expression of TNF alpha, PEPCK-C and PPAR alpha, and no significant 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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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