Fimasartan, anti-hypertension drug, suppressed inducible nitric oxide synthase expressions via nuclear factor-kappa B and activator protein-1 inactivation.

Abstract

Since inhibition of angiotensin II type 1 (AT1) receptor reduces chronic inflammation associated with hypertension, we evaluated the anti-inflammatory potential and the underlying mechanism of fimasartan, a Korean Food and Drug Administration approved anti-hypertension drug, in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Fimasartan suppressed the expressions of inducible nitric oxide synthase (iNOS) by down-regulating its transcription, and subsequently inhibited the productions of nitric oxide (NO). In addition, fimasartan attenuated LPS-induced transcriptional and DNA-binding activities of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). These reductions were accompanied by parallel reductions in the nuclear translocation of NF-κB and AP-1. Taken together, our data suggest that fimasartan down-regulates the expression of the iNOS in macrophages via NF-κB and AP-1 inactivation.

• Authors: Suran Ryu, Ji-Sun Shin, Young-Wuk Cho, Hyoung Kook Kim, Soo Heui Paik, Joo Han Lee, Yong Ha Chi, Ji Han Kim, Je Hak Kim, Kyung-Tae Lee
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 36 Issue 3 Pg. 467-74 ( 2013) ISSN: 1347-5215 [Electronic] Japan
• PMID: 23449332 (Publication Type: Journal Article)

Chemical References

• Antihypertensive Agents
• Biphenyl Compounds
• Lipopolysaccharides
• NF-kappa B
• Pyrimidines
• Tetrazoles
• Transcription Factor AP-1
• Nitric Oxide
• Nitric Oxide Synthase Type II
• fimasartan

Topics

• Animals
• Antihypertensive Agents (pharmacology)
• Biphenyl Compounds (pharmacology)
• Cells, Cultured
• Lipopolysaccharides (pharmacology)
• Macrophages (drug effects, metabolism)
• Mice
• NF-kappa B (antagonists & inhibitors)
• Nitric Oxide (biosynthesis)
• Nitric Oxide Synthase Type II (antagonists & inhibitors)
• Pyrimidines (pharmacology)
• Tetrazoles (pharmacology)
• Transcription Factor AP-1 (antagonists & inhibitors)