Suppression of endotoxin-induced renal tumor necrosis factor-alpha and interleukin-6 mRNA by renin-angiotensin system inhibitors.
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 inhibitor suppressed renal IL-6 and TNF-alpha production and may prevent cytokine-induced renal damage during endotoxemia.
Niimi
Ryo
R
Department of Paediatrics, Teikyo University School of Medicine, Tokyo, Japan.
Nakamura
Akio
A
Yanagawa
Yukishige
Y
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D015152:Blotting, Northern; D016207:Cytokines / Q000235:genetics; D004656:Enalapril / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D012083:Renin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics*; D000093242:Interleukin-6 Inhibitors
D000804:Angiotensin II; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000808:Angiotensinogen; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D016207:Cytokines; D004656:Enalapril; D004731:Endotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D012083:Renin; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C077793:candesartan cilexetil