Suppression of Endotoxin-Induced Renal Tumor Necrosis Factor-α and Interleukin-6 mRNA by Renin-Angiotensin System Inhibitors

Niimi, Ryo; Yanagawa, Yukishige

doi:10.1254/jjp.88.139

Cited by 27 publications

(17 citation statements)

References 34 publications

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“…The results presented in this report are consistent with studies that demonstrated similar cytokine-modulating effects of ACE inhibitors in various experimental models 13,40. One could argue, however, that the effects of enalapril treatment on the cytokine expression profiles observed were due to a direct effect of blocking Ang II activity or as a consequence of reduced hypertension.…”

Section: Discussionsupporting

confidence: 92%

The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats

Dalpiaz

Lamas

Caliman

et al. 2013

Braz J Med Biol Res

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Sex hormones modulate the action of both cytokines and the renin-angiotensin system. However, the effects of angiotensin I-converting enzyme (ACE) on the proinflammatory and anti-inflammatory cytokine levels in male and female spontaneously hypertensive rats (SHR) are unclear. We determined the relationship between ACE activity, cytokine levels and sex differences in SHR. Female (F) and male (M) SHR were divided into 4 experimental groups each (n = 7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage), castrated + vehicle, and castrated + enalapril. Treatment began 21 days after castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE activity than female rats. Castration reduced serum ACE in males but did not affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV = 16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV = 12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levels were higher in females than in males. Ovariectomy reduced all cytokine levels and orchiectomy reduced IL-6 but increased IL-10 concentrations in males. Castration eliminated the differences in all inflammatory cytokine levels (IL-6 and TNF-α) between males and females. Enalapril increased IL-10 in all groups and reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects.

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Section: Discussionsupporting

confidence: 92%

The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats

Dalpiaz

Lamas

Caliman

et al. 2013

Braz J Med Biol Res

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“…30,31) In addition, recent studies have demonstrated that angiotensin-converting enzyme inhibitors suppress the LPS-induced production of proinflammatory cytokines, such as IL-1, IL-6 and TNF-a in human peripheral mononuclear cells and rat kidney. [32][33][34] Losartan inhibits the LPS-induced apoptosis of rat ventricular myocytes. 35) Ang II induces the production of IL-6 by rat vascular smooth muscle cells and that of TNF-a by rat renal tubules.…”

Section: Discussionmentioning

confidence: 99%

The Lipopolysaccharide-Induced Up-Regulation of Bradykinin B2-Receptor in the Mouse Heart Is Mediated by Tumor Necrosis Factor-.ALPHA. and Angiotensin II

Yayama

Hiyoshi

Sugiyama

et al. 2006

Biological & Pharmaceutical Bulletin

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Lipopolysaccharide (LPS) is one of the most potent and widely studied signal molecules involved in the initiation of septic shock. LPS activates multiple cells to release cytokines (such as tumor necrosis factor (TNF)-a, interleukin (IL)-1b, IL-6, interferon-g), nitric oxide (NO), metabolites of arachidonic acid, platelet-activating factor, and kinins. 1,2) These mediators contribute to the subsequent cellular responses, including increased vascular permeability, the generation of toxic oxygen metabolites, the generation of microthrombi, systemic hypotension, and organ failure.3)The presence and functional relevance of the kallikreinkinin system in the heart are firmly established. 4) Kinins, liberated by kallikrein from substrate kininogen, stimulate the release of NO and prostacyclin through the activation of bradykinin B 2 -receptor. This action opposes angiotensin II (Ang II)-induced vasoconstriction and exerts anti-ischemic, antiproliferative and antiatherosclerotic effects, preserving myocardial stores of energy-rich phosphates and glycogen. 5)Furthermore, stimulation of Ang II type 2 (AT 2 -) receptor present in myocardium attenuates the AT 1 -medicated cardiac hypertrophy and interstitial fibrosis through the B 2 -receptordependent mechanisms.6) The activation of B 2 -receptor in cardiac myocytes involves the cardioprotective effect of angiotensin-converting enzyme inhibitors and AT 1 -receptor antagonists in heart failure. 7)The presence of two subtypes of bradykinin receptors, B 1 -and B 2 -receptors, has been identified in the myocardium, 8) although B 1 -receptors are detectable after the induction of inflammation. LPS induces B 1 -receptors in the rat heart. 9)However, B 1 -receptor blockade does not attenuate the LPSinduced mortality.10) In contrast, it has been demonstrated that the administration of B 2 -receptor antagonists shows beneficial effects, i.e., increased survival rates and improved hemodynamic parameters in a model of endotoxin shock. [11][12][13][14] However, whether the expression of the B 2 -receptor in the heart is altered during sepsis is unknown. Therefore, the present study has been undertaken in mice to elucidate 1) whether the cardiac expression of B 2 -receptor mRNA is altered by LPS, and 2) which mediators are involved in the LPSinduced changes in cardiac B 2 -receptor mRNA expression. MATERIALS AND METHODS MaterialsThe following chemicals were obtained from commercial sources: LPS (Staphylococcus typhosa 0901) from Difco (Detroit, MI, U.S.A.); Ang II from Peptide Institute (Osaka, Japan); TNF-a, IL-1b and IL-6 from Sigma (St Louis, MO, U.S.A.), endothelin-1 (Nacalai Tesque); losartan (AT 1 -receptor antagonist; Funakoshi, Osaka, Japan), PD123319 (AT 2 -receptor antagonist; Wako Chemicals, Kyoto, Japan).Animal Treatment All animal experiments were performed according to the guidelines of the Kobe Gakuin University Experimental Animal Care and Use Committee. Male ddY mice, aged 6-8 weeks, 28-32 g (Japan SLC, Hamamatsu, Japan) were used in this study. Mice were injected with ...

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“…For example, in vitro studies have suggested that ANG II is involved in the production of proinflammatory cytokines from LPS-stimulated leukocytes (Schindler et al, 1995;Peeters et al, 1998). Moreover, application of ANG II onto cultured mesangial cells results in the production of another cytokine, IL-6 (Moriyama et al, 1995), and systemic administration of LPS increases renal IL-6 production, an effect that can be inhibited by an ACE inhibitor or an AT 1 receptor antagonist (Niimi et al, 2002). Finally, we recently demonstrated contributions of ANG II and its AT 1 receptor to LPSinduced hepatic IL-1␤ production in vivo (Miyoshi et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Central Injection of Angiotensin-Converting Enzyme Inhibitor and the Angiotensin Type 1 Receptor Antagonist on the Induction by Lipopolysaccharide of Fever and Brain Interleukin-1β Response in Rats

Shimizu

Miyoshi²,

Matsumoto³

et al. 2003

J Pharmacol Exp Ther

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We recently reported an involvement of peripheral angiotensin II (ANG II) in the development of both the fever and the peripheral interleukin (IL)-1␤ production induced in rats by a systemic injection of lipopolysaccharide (LPS). The present study was performed to investigate whether brain ANG II contributes to the fever and IL-1␤ production in the rat brain induced by i.c.v. injection of LPS. LPS (0.2 and 2 g i.c.v.) induced dose-related fevers and increases in the brain (hypothalamus, hippocampus, and cerebellum) concentrations of IL-1␤. These effects were significantly inhibited by i.c.v. administration of either an angiotensin-converting-enzyme (ACE) inhibitor or an angiotensin type 1 (AT 1 ) receptor antagonist. By contrast, the ACE inhibitor had no effect on the IL-1␤ (i.c.v.)-induced fever, whereas the AT 1 receptor antagonist enhanced (rather than reduced) it. The AT 1 receptor antagonist had no effect on the brain levels of prostaglandin E 2 in rats given an i.c.v. injection of IL-1␤. These results suggest that in rats, brain ANG II and AT 1 receptors are involved in the LPS-induced production of brain IL-1␤, thus contributing to the fever induced by the presence of LPS within the brain.Angiotensin II (ANG II), a bioactive peptide well known to play an important role in blood pressure and body fluid regulation, seems to participate in inflammatory responses, too. For example, an angiotensin-convertingenzyme (ACE) inhibitor has been shown to have an antiinflammatory effect (Godsel et al., 2003). Furthermore, ANG II and ANG II type 1 (AT 1 ) receptors are involved in cardiovascular inflammation, such as monocyte infiltration (Usui et al., 2000). Recently, we reported results suggesting that ANG II is involved in the development of the fever (an inflammation-related response) induced by i.v. injection of lipopolysaccharide (LPS, 2 g/kg) in euhydrated rats as well as in dehydrated rats (in which the secretion of ANG II is elevated) (Watanabe et al., 2000). In fact, the LPS-induced fever seen in that study was significantly attenuated by an ACE inhibitor, injected i.v. Because, as the first step in fever induction the pyrogenic/ proinflammatory cytokine interleukin (IL)-1 is released from macrophages after their stimulation by LPS (Kluger, 1991;Dinarello, 1999), we speculated that ANG II might contribute to the LPS-induced peripheral production of IL-1. Indeed, i.v. injection of LPS increases the liver concentration of IL-1␤ in dehydrated rats, and this effect can be significantly attenuated by an ACE inhibitor or by an AT 1 receptor antagonist, in each case given i.v. (Miyoshi et al., 2003). However, we found that an i.v. injection of LPS (2 g/kg) did not induce any detectable changes in the brain level of IL-1␤ (our unpublished observations). It seemed likely from these results that peripheral ANG II is involved in the development of the peripheral production of IL-1␤ (induced by LPS). The brain has its own renin-angiotensin system and its own AT 1 receptors that play important roles in blood press...

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Suppression of Endotoxin-Induced Renal Tumor Necrosis Factor-α and Interleukin-6 mRNA by Renin-Angiotensin System Inhibitors

Cited by 27 publications

References 34 publications

The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats

The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats

The Lipopolysaccharide-Induced Up-Regulation of Bradykinin B2-Receptor in the Mouse Heart Is Mediated by Tumor Necrosis Factor-.ALPHA. and Angiotensin II

The Effect of Central Injection of Angiotensin-Converting Enzyme Inhibitor and the Angiotensin Type 1 Receptor Antagonist on the Induction by Lipopolysaccharide of Fever and Brain Interleukin-1β Response in Rats

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