Suppression of endotoxin-induced renal tumor necrosis factor-alpha and interleukin-6 mRNA by renin-angiotensin system inhibitors

Japanese Journal of Pharmacology
Ryo NiimiYukishige Yanagawa

Abstract

The present study was designed to clarify the role of angiotensin II (Ang II) in modulating renal tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) production and to investigate the effect of one dose of Ang II inhibitor on cytokines production following lipopolysaccharide (LPS) to cause endotoxemia. Two studies were performed: 1) Ang II was infused intravenously at a rate of 0.2 microg/kg per minute for 4 h in rats and then kidneys were collected to assay TNF-alpha and IL-6 mRNA levels; 2) Four-week-old Wistar rats pre-treated with angiotensin-converting enzyme inhibitor, enalapril, or type I Ang II-receptor antagonist, TCV-116, were injected with LPS (0.1, 0.5, 1.0 mg, i.p.), and then 2 or 4 h later, kidneys were collected to assay TNF-alpha, IL-6, renin and angiotensinogen mRNA levels. After a 4-h intravenous infusion of Ang II, renal TNF-alpha or IL-6 mRNA level significantly increased 1.9-fold or 2.1-fold (each P<0.05) to the control level, respectively. LPS stimulated TNF-alpha, IL-6 and angiotensinogen mRNA levels in the kidney but in rats given enalapril or TCV-116, LPS-induced IL-6 and TNF-alpha mRNA levels were completely suppressed (each P<0.05). This suggests that a single dose of renin-angiotensin system i...Continue Reading

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Citations

Feb 12, 2014·International Journal of Medical Sciences·Kazi RafiqAkira Nishiyama
Nov 2, 2002·Kidney International. Supplement·Marta Ruiz-OrtegaJesus Egido
Sep 17, 2005·Pharmacotherapy·Nigel J Dagenais, Fakhreddin Jamali
Oct 18, 2011·Research in Veterinary Science·Augusta ZannoniMonica Forni
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Apr 6, 2007·American Journal of Physiology. Renal Physiology·Akanksha GuptaBrian W Grinnell
Nov 14, 2015·Clinical and Experimental Nephrology·Shigeru TanakaKazuhiko Tsuruya
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Nov 5, 2002·The American Journal of Pathology·Dominik N MullerFriedrich C Luft

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