Role of asymmetric dimethylarginine in rat acute lung injury induced by acute ischemic kidney injury

Ma,Tao; Liu,Xiaowei; Liu,Zhi

doi:10.3892/mmr.2015.3619

Role of asymmetric dimethylarginine in rat acute lung injury induced by acute ischemic kidney injury

Authors:
- Tao Ma
- Xiaowei Liu
- Zhi Liu
View Affiliations

Affiliations: Department of Emergency Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: April 15, 2015 https://doi.org/10.3892/mmr.2015.3619
Pages: 1923-1928

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to establish a rat model of acute ischemic kidney injury by continually occluding the bilateral renal artery and renal veins, as well as to examine the role of asymmetric dimethylarginine (ADMA) in acute lung injury (ALI) induced by acute kidney injury (AKI). In total, 45 male Wistar rats were randomly divided into the control, AKI and AKI + SB203580 groups. The enzyme‑linked immunosorbent assay method was used to assess the plasma levels of ADMA in each group. The activation of p38 mitogen‑activated protein kinase (MAPK) and heat shock protein 27 (HSP27) was detected using western blot analysis. Immunofluorescence analyses of filamentous actin (F‑actin) and globular actin (G‑actin) were performed. The levels of plasma ADMA and the permeability index in the AKI group were significantly higher than those in the control and AKI + SB203580 groups. The expression of phosphorylated p38 (p‑p38) and p‑HSP27 was significantly higher in the AKI and AKI + SB203580 groups compared with the control group. The AKI group also demonstrated a higher expression of p‑p38 and p‑HSP27 than the AKI + SB203580 group. The expression of F‑actin was more marked in the AKI group than in the control and AKI + SB203580 groups. The F‑/G‑actin ratio in the AKI group was also higher compared with that in the control and AKI + SB203580 groups. The results from the present study indicated that plasma ADMA levels may be a good biomarker for AKI‑induced ALI. In addition, the p38 MAPK/HSP27 pathway is important in modulating the levels of ADMA.

View Figures

View References

1	Liu KD, Himmelfarb J, Paganini E, et al: Timing of initiation of dialysis in critically ill patients with acute kidney injury. Clin J Am Soc Nephrol. 1:915–919. 2006. View Article : Google Scholar
2	Himmelfarb J and Ikizler TA: Acute kidney injury: changing lexicography, definitions, and epidemiology. Kidney Int. 71:971–976. 2007. View Article : Google Scholar : PubMed/NCBI
3	Akcan-Arikan A, Zappitelli M, Loftis LL, et al: Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int. 71:1028–1035. 2007. View Article : Google Scholar : PubMed/NCBI
4	Mehta RL, Kellum JA, Shah SV, et al: Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 11:R312007. View Article : Google Scholar : PubMed/NCBI
5	Schwenger V, Weigand MA, Hoffmann O, et al: Sustained low efficiency dialysis using a single-pass batch system in acute kidney injury – a randomized interventional trial: the REnal Replacement Therapy Study in Intensive Care Unit PatiEnts. Crit Care. 16:R1402012. View Article : Google Scholar
6	Martin A and Acierno MJ: Continuous renal replacement therapy in the treatment of acute kidney injury and electrolyte disturbances associated with acute tumor lysis syndrome. J Vet Intern Med. 24:986–989. 2010. View Article : Google Scholar : PubMed/NCBI
7	Kuchnicka K and Maciejewski D: Ventilator-associated lung injury. Anaesthesiol Intensive Ther. 45:164–170. 2013. View Article : Google Scholar : PubMed/NCBI
8	Hassoun HT, Grigoryev DN, Lie ML, et al: Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrectomy. Am J Physiol Renal Physiol. 293:F30–F40. 2007. View Article : Google Scholar : PubMed/NCBI
9	White LE, Chaudhary R, Moore LJ, et al: Surgical sepsis and organ crosstalk: the role of the kidney. J Surg Res. 167:306–315. 2011. View Article : Google Scholar : PubMed/NCBI
10	Böger RH: Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, explains the ‘L-arginine paradox’ and acts as a novel cardiovascular risk factor. J Nutr. 134:2842S–2847S. 2004.
11	Vallance P and Leiper J: Cardiovascular biology of the asymmetric dimethylarginine:dimethylarginine dimethyl-aminohydrolase pathway. Arterioscler Thromb Vasc Biol. 24:1023–1030. 2004. View Article : Google Scholar : PubMed/NCBI
12	Palm F, Onozato ML, Luo Z, et al: Dimethylarginine dimethyl-aminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems. Am J Physiol Heart Circ Physiol. 293:H3227–H3245. 2007. View Article : Google Scholar : PubMed/NCBI
13	Fliser D, Kronenberg F, Kielstein JT, et al: Asymmetric dimethyl arginine and progression of chronic kidney disease: the mild to moderate kidney disease study. J Am Soc Nephrol. 16:2456–2461. 2005. View Article : Google Scholar : PubMed/NCBI
14	Wang LY, Zhang DL, Zheng JF, et al: Apelin-13 passes through the ADMA-damaged endothelial barrier and acts on vascular smooth muscle cells. Peptides. 32:2436–2443. 2011. View Article : Google Scholar : PubMed/NCBI
15	Chertow GM, Burdick E, Honour M, et al: Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 16:3365–3370. 2005. View Article : Google Scholar : PubMed/NCBI
16	Togel F, Weiss K, Yang Y, et al: Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury. Am J Physiol Renal Physiol. 292:F1626–F1635. 2007. View Article : Google Scholar : PubMed/NCBI
17	Hoste EA and Schurgers M: Epidemiology of acute kidney injury: how big is the problem? Crit Care Med. 36:S146–S151. 2008. View Article : Google Scholar : PubMed/NCBI
18	Coca SG, Yusuf B, Shlipak MG, et al: Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 53:961–973. 2009. View Article : Google Scholar : PubMed/NCBI
19	Ma T and Liu Z: Functions of aquaporin 1 and alpha-epithelial Na⁺ channel in rat acute lung injury induced by acute ischemic kidney injury. Int Urol Nephrol. 45:1187–1196. 2013. View Article : Google Scholar
20	Vadasz I, Raviv S and Sznajder JI: Alveolar epithelium and Na,K-ATPase in acute lung injury. Intensive Care Med. 33:1243–1251. 2007. View Article : Google Scholar : PubMed/NCBI
21	Banan A, Choudhary S, Zhang Y, et al: Oxidant-induced intestinal barrier disruption and its prevention by growth factors in a human colonic cell line: role of the microtubule cytoskeleton. Free Radic Biol Med. 28:727–738. 2000. View Article : Google Scholar : PubMed/NCBI
22	Rosenthal KS, Perez R and Hodnichak C: Inhibition of herpes simplex virus type 1 penetration by cytochalasins B and D. J Gen Virol. 66:1601–1605. 1985. View Article : Google Scholar : PubMed/NCBI
23	Fujiwara I, Takahashi S, Tadakuma H, et al: Microscopic analysis of polymerization dynamics with individual actin filaments. Nat Cell Biol. 4:666–673. 2002. View Article : Google Scholar : PubMed/NCBI
24	Weber NC, Toma O, Wolter JI, et al: Mechanisms of xenon- and isoflurane-induced preconditioning – a potential link to the cytoskeleton via the MAPKAPK-2/HSP27 pathway. Br J Pharmacol. 146:445–455. 2005. View Article : Google Scholar : PubMed/NCBI
25	Loktionova SA and Kabakov AE: Protein phosphatase inhibitors and heat preconditioning prevent Hsp27 dephosphor-ylation, F-actin disruption and deterioration of morphology in ATP-depleted endothelial cells. FEBS Lett. 433:294–300. 1998. View Article : Google Scholar : PubMed/NCBI
26	Rousseau S, Houle F, Landry J, et al: p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganization and cell migration in human endothelial cells. Oncogene. 15:2169–2177. 1997. View Article : Google Scholar : PubMed/NCBI
27	Xiong Z, Wang Y, Gong W, et al: Expression of Hsp27 correlated with rat detrusor contraction after acute urinary retention. Mol Cell Biochem. 381:257–265. 2013. View Article : Google Scholar : PubMed/NCBI