Nitric Oxide Protects against Ischemic Acute Renal Failure through the Suppression of Renal Endothelin-1 Overproduction

Kurata, Hayato; Takaoka, Masanori; Kubo, Yasuhiro; Katayama, Tomoaki; Tsutsui, Hidenobu; Takayama, Junji; Matsumura, Yasuo

doi:10.1097/01.fjc.0000166314.38258.a8

Cited by 13 publications

(9 citation statements)

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“…Arrow indicates nitrotyrosine (magnification, ϫ200). against ischemia/reperfusion-induced renal dysfunction and tissue injury, at least in part, through the suppression of endothelin-1 production (Kurata et al, 2004). The overproduction of this peptide in the postischemic kidney is known to be one of the major causal factors of this disease (Wilhelm et al, 1999;Matsumura et al, 2000).…”

Section: Figmentioning

confidence: 99%

RETRACTION: Opposite Effects of Pre- and Postischemic Treatments with Nitric Oxide Donor on Ischemia/Reperfusion-Induced Renal Injury

Nakajima

Ueda

Takaoka

et al. 2005

J Pharmacol Exp Ther

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We have demonstrated previously that preischemic treatment with FK409 [(Ϯ)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide], a spontaneous nitric oxide (NO) donor, markedly improves ischemia/reperfusion-induced renal injury. However, there is conflicting information (renoprotective or cytotoxic) as to the contribution of NO to ischemic acute renal failure (ARF). In the present study, we investigated the effect of postischemic treatment with FK409 (1, 3, and 10 mg/kg i.v.) at 6 h after reperfusion on ischemic ARF, in comparison with the preischemic treatment effect. Ischemic ARF was induced by clamping of the left renal artery and vein for 45 min, followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function in ARF rats markedly decreased at 24 h after reperfusion. Histopathological examination of the kidney of ARF rats revealed severe renal damage. In contrast to the renoprotective effect by preischemic treatment, postischemic treatment with FK409 aggravated the ischemia/reperfusion-induced renal dysfunction and histological damage. Immunohistochemical analysis of renal sections obtained from ARF rats revealed positive staining for nitrotyrosine, a biomarker of peroxynitrite formation, in injured tubular cells, and more intense staining was observed in renal tissues from the animals that received postischemic treatment with FK409. On the other hand, the formation of nitrotyrosine, neutrophil infiltration into renal tissues, and renal superoxide production, all of which were enhanced in ARF rats, were efficiently attenuated by the preischemic treatment with FK409. These results demonstrate that, although preischemic treatment with an NO donor is renoprotective, postischemic treatment with the same agent aggravates the ischemia/ reperfusion-induced renal injury, probably through peroxynitrite overproduction.

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Section: Figmentioning

confidence: 99%

RETRACTION: Opposite Effects of Pre- and Postischemic Treatments with Nitric Oxide Donor on Ischemia/Reperfusion-Induced Renal Injury

Nakajima

Ueda

Takaoka

et al. 2005

J Pharmacol Exp Ther

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“…In studies resembling acute renal failure, pretreatment with CB1 agonists prevented tubular necrosis in the renal medulla after ischemia-reperfusion in mice (7). Since stimulation of NOS and NO production also prevents renal damage after ischemia-reperfusion (16), it is likely that the protective effects derived from CB1 receptors activation could be also mediated by NO. This effect has also been seen in other cell types.…”

Section: Discussionmentioning

confidence: 99%

Anandamide inhibits transport-related oxygen consumption in the loop of Henle by activating CB1 receptors

Silva

Atchison

Juncos³

et al. 2013

American Journal of Physiology-Renal Physiology

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The energy required for active Na chloride reabsorption in the thick ascending limb (TAL) depends on oxygen consumption and oxidative phosphorylation (OXP). In other cells, Na transport is inhibited by the endogenous cannabinoid anandamide through the activation of the cannabinoid receptors (CB) type 1 and 2. However, it is unclear whether anandamide alters TAL transport and the mechanisms that could be involved. We hypothesized that anandamide inhibits TAL transport via activation of CB1 receptors and NO. For this, we measured oxygen consumption (QO 2 ) in TAL suspensions to monitor the anandamide effects on transport and OXP. Anandamide reduced QO 2 in a concentration-dependent manner. During Na-K-2Cl cotransport and Na/H exchange inhibition, anandamide did not inhibit TAL QO 2 . To test the role of the cannabinoid receptors, we used specific agonists and antagonists of CB1 and CB2 receptors. The CB1-selective agonist WIN55212-2 reduced QO 2 in a concentration-dependent manner. Also, the CB1 receptor antagonist rimonabant blocked the effect of anandamide on QO 2 . In contrast, the CB2-selective agonist JHW-133 had no effect on QO 2 , while the CB2 receptor antagonist AM-630 failed to block the anandamide effects on Q O 2 . To confirm these results, we measured CB1 and CB2 receptor expression and only CB1 expression was detected. Because CB1 receptors are strong nitric oxide synthase (NOS) stimulators and NO inhibits transport in TALs, we evaluated the role of NO. Anandamide stimulated NO production and the NOS inhibitor N G -nitro-L-arginine methyl ester blocked the anandamide effects on Q O 2 . We conclude that anandamide inhibits TAL Na transport-related Q O 2 via activation of CB1 receptor and NOS.

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“…Endogenous NO production has a protective effect in experimental AKI where it promotes vasodilatation and reduces inflammation [68][69][70] and manipulation of NO pathways is an attractive therapeutic option. In an early phase three study, the clinical benefit of the NO donor SNP was marginal, with only a small and non-clinically significant improvement in renal function however [45].…”

Section: Nitric Oxide Donorsmentioning

confidence: 99%

Pharmacological therapies for the prevention of acute kidney injury following cardiac surgery: a systematic review

et al. 2011

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Post-cardiac surgery acute kidney injury (AKI) is common and is associated with a significant increase in morbidity and mortality. We aimed to systematically review randomised trials that assessed the renoprotective utility of pharmacological agents in patients undergoing cardiac surgery. We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials comparing renoprotective pharmacological interventions with control in adult patients undergoing cardiac surgery with cardiopulmonary bypass. We extracted data for mortality, need for renal replacement therapy (RRT), incidence of AKI, and creatinine clearance at 24-48 h. About 49 randomised controlled trials involving 4605 patients were included. Pharmacological interventions included dopamine, fenoldopam, calcium channel antagonists, natriuretic peptides, diuretics, and N-acetylcysteine. Most trials were of poor quality, with small sample sizes, under-reporting of randomisation procedure, allocation concealment and method of blinding. No pharmacological intervention significantly reduced mortality. Fenoldopam and Atrial Natriuretic Peptide (ANP) reduced the need for renal replacement therapy by 5% (NNT 20, 95% CI 11.3, 83.0) and 3.5% (NNT 29, 95% CI 17.1, 84.4), respectively. Brain Natriuretic Peptide resulted in a 10% reduction in the incidence of AKI (NNT 11, 95% CI 6.2, 32.0). Dopamine caused a significant reduction in creatinine clearance (-4.26 ml/min, 95% CI -7.14, -1.39). The quality of studies that have assessed pharmacological renoprotective agents in cardiac surgery is generally poor. Fenoldopam, ANP and BNP show evidence of renoprotection. Randomised studies evaluating the effect of novel renoprotective agents that are powered to detect clinically relevant differences in outcomes are required.

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Nitric Oxide Protects against Ischemic Acute Renal Failure through the Suppression of Renal Endothelin-1 Overproduction

Cited by 13 publications

References 0 publications

RETRACTION: Opposite Effects of Pre- and Postischemic Treatments with Nitric Oxide Donor on Ischemia/Reperfusion-Induced Renal Injury

RETRACTION: Opposite Effects of Pre- and Postischemic Treatments with Nitric Oxide Donor on Ischemia/Reperfusion-Induced Renal Injury

Anandamide inhibits transport-related oxygen consumption in the loop of Henle by activating CB1 receptors

Pharmacological therapies for the prevention of acute kidney injury following cardiac surgery: a systematic review

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