title: ANG II is involved in the LPS-induced production of proinflammatory cytokines in dehydrated rats.
abstract: We have previously reported results that led us to speculate that ANG II is involved in the LPS-induced production of proinflammatory cytokines, especially under dehydrated conditions. To test this possibility, in this study we examined the effects of an angiotensin-converting enzyme (ACE) inhibitor and an antagonist of the type-1 ANG II receptor (AT(1) receptor) on the LPS-induced production of the proinflammatory cytokines IL-1 and IL-6 in dehydrated rats. A single intravenous injection of LPS induced a marked increase in the expression of IL-1beta mRNA in the liver, an effect that was significantly attenuated by pretreatment with the ACE inhibitor. Furthermore, the ACE inhibitor reduced the LPS-induced increase in the hepatic concentration of IL-1beta protein. When the AT(1)-receptor antagonist was given intravenously before the LPS, the increase in the hepatic concentration of IL-1beta was significantly reduced. Finally, the ACE inhibitor reduced the LPS-induced increase in the plasma concentration of IL-6. These results represent the first in vivo evidence that ANG II and its AT(1) receptor play important roles in the production of proinflammatory cytokines that is induced by LPS under dehydrated conditions.
authors.affiliation: The Department of Physiology, Tottori University Faculty of Medicine, Yonago, Tottori 683, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Miyoshi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Nagata
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Imoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Goto
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishida
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D003681:Dehydration / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007375:Interleukin-1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017706:Lisinopril / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D000804:Angiotensin II; D017706:Lisinopril; D019808:Losartan