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Interaction among nitric oxide, reactive oxygen species, and antioxidants during endotoxemia-related acute renal failure.
Am J Physiol Renal Physiol. 2003 Mar; 284(3):F532-7.AJ

Abstract

Acute renal failure (ARF) during sepsis is associated with increased nitric oxide (NO) and oxygen radicals, including superoxide (O(2)(-)). Because O(2)(-) reacts with NO in a rapid manner, it plays an important role in modulating NO levels. Therefore, scavenging of O(2)(-) by superoxide dismutase (SOD) may be critical for preserving NO bioavailability. In mice, substantial renal extracellular SOD (EC-SOD) expression implies its important role in scavenging O(2)(-) in the kidney. We hypothesized that during endotoxemic ARF, EC-SOD is decreased in the kidney, resulting in increased O(2)(-) and thus decreased vascular NO bioavailability with resultant renal vasoconstriction and ARF. In the present study, normotensive endotoxemic ARF was induced in mice using lipopolysaccharide (LPS; 5 mg/kg ip). Sixteen hours after LPS, glomerular filtration rate (GFR; 50 +/- 16 vs. 229 +/- 21 microl/min, n = 8, P < 0.01) and renal blood flow (RBF; 0.61 +/- 0.10 vs. 0.86 +/- 0.05 ml/min, n = 8, P < 0.05) were subsequently decreased. EC-SOD mRNA and protein expression in endotoxemic kidneys were decreased at 16 h compared with controls. A catalytic antioxidant, metalloporphyrin, reversed the deleterious effects of endotoxemia on renal function as GFR (182 +/- 40 vs. 50 +/- 16 microl/min, n = 6, P < 0.01) and RBF (1.08 +/- 0.10 vs. 0.61 +/- 0.10 ml/min, n = 6, P < 0.05) were preserved. Similar results were obtained with tempol, a chemically dissimilar antioxidant. Specific inhibition of inducible nitric oxide synthase (iNOS), l-N(6)-(1-iminoethyl)-lysine, reversed the renal protective effect on GFR and RBF observed with antioxidant treatment during endotoxemia. In summary, renal EC-SOD expression is decreased during endotoxemia. Antioxidant therapy preserved GFR and RBF during endotoxemia. The reversal of this protective effect by inhibition of iNOS suggests the importance of the bioavailability of NO for preservation of renal function during early endotoxemia.

Authors+Show Affiliations

Wang W
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Jittikanont S
No affiliation info available
Falk SA
No affiliation info available
Li P
No affiliation info available
Feng L
No affiliation info available
Gengaro PE
No affiliation info available
Poole BD
No affiliation info available
Bowler RP
No affiliation info available
Day BJ
No affiliation info available
Crapo JD
No affiliation info available
Schrier RW
No affiliation info available

MeSH

Acute Kidney InjuryAnimalsAntioxidantsBlood PressureDisease Models, AnimalEndotoxemiaEnzyme InhibitorsExtracellular SpaceFree Radical ScavengersGlomerular Filtration RateKidneyLipopolysaccharidesMaleMiceMice, Inbred C57BLNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIRNA, MessengerReactive Oxygen SpeciesRenal Blood Flow, EffectiveSuperoxide DismutaseSurvival Rate

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12556364

Citation

Wang, Wei, et al. "Interaction Among Nitric Oxide, Reactive Oxygen Species, and Antioxidants During Endotoxemia-related Acute Renal Failure." American Journal of Physiology. Renal Physiology, vol. 284, no. 3, 2003, pp. F532-7.
Wang W, Jittikanont S, Falk SA, et al. Interaction among nitric oxide, reactive oxygen species, and antioxidants during endotoxemia-related acute renal failure. Am J Physiol Renal Physiol. 2003;284(3):F532-7.
Wang, W., Jittikanont, S., Falk, S. A., Li, P., Feng, L., Gengaro, P. E., Poole, B. D., Bowler, R. P., Day, B. J., Crapo, J. D., & Schrier, R. W. (2003). Interaction among nitric oxide, reactive oxygen species, and antioxidants during endotoxemia-related acute renal failure. American Journal of Physiology. Renal Physiology, 284(3), F532-7.
Wang W, et al. Interaction Among Nitric Oxide, Reactive Oxygen Species, and Antioxidants During Endotoxemia-related Acute Renal Failure. Am J Physiol Renal Physiol. 2003;284(3):F532-7. PubMed PMID: 12556364.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interaction among nitric oxide, reactive oxygen species, and antioxidants during endotoxemia-related acute renal failure. AU - Wang,Wei, AU - Jittikanont,Suparoek, AU - Falk,Sandor A, AU - Li,Ping, AU - Feng,Lili, AU - Gengaro,Patricia E, AU - Poole,Brian D, AU - Bowler,Russell P, AU - Day,Brian J, AU - Crapo,James D, AU - Schrier,Robert W, PY - 2003/1/31/pubmed PY - 2003/3/13/medline PY - 2003/1/31/entrez SP - F532 EP - 7 JF - American journal of physiology. Renal physiology JO - Am J Physiol Renal Physiol VL - 284 IS - 3 N2 - Acute renal failure (ARF) during sepsis is associated with increased nitric oxide (NO) and oxygen radicals, including superoxide (O(2)(-)). Because O(2)(-) reacts with NO in a rapid manner, it plays an important role in modulating NO levels. Therefore, scavenging of O(2)(-) by superoxide dismutase (SOD) may be critical for preserving NO bioavailability. In mice, substantial renal extracellular SOD (EC-SOD) expression implies its important role in scavenging O(2)(-) in the kidney. We hypothesized that during endotoxemic ARF, EC-SOD is decreased in the kidney, resulting in increased O(2)(-) and thus decreased vascular NO bioavailability with resultant renal vasoconstriction and ARF. In the present study, normotensive endotoxemic ARF was induced in mice using lipopolysaccharide (LPS; 5 mg/kg ip). Sixteen hours after LPS, glomerular filtration rate (GFR; 50 +/- 16 vs. 229 +/- 21 microl/min, n = 8, P < 0.01) and renal blood flow (RBF; 0.61 +/- 0.10 vs. 0.86 +/- 0.05 ml/min, n = 8, P < 0.05) were subsequently decreased. EC-SOD mRNA and protein expression in endotoxemic kidneys were decreased at 16 h compared with controls. A catalytic antioxidant, metalloporphyrin, reversed the deleterious effects of endotoxemia on renal function as GFR (182 +/- 40 vs. 50 +/- 16 microl/min, n = 6, P < 0.01) and RBF (1.08 +/- 0.10 vs. 0.61 +/- 0.10 ml/min, n = 6, P < 0.05) were preserved. Similar results were obtained with tempol, a chemically dissimilar antioxidant. Specific inhibition of inducible nitric oxide synthase (iNOS), l-N(6)-(1-iminoethyl)-lysine, reversed the renal protective effect on GFR and RBF observed with antioxidant treatment during endotoxemia. In summary, renal EC-SOD expression is decreased during endotoxemia. Antioxidant therapy preserved GFR and RBF during endotoxemia. The reversal of this protective effect by inhibition of iNOS suggests the importance of the bioavailability of NO for preservation of renal function during early endotoxemia. SN - 1931-857X UR - https://www.unboundmedicine.com/medline/citation/12556364/Interaction_among_nitric_oxide_reactive_oxygen_species_and_antioxidants_during_endotoxemia_related_acute_renal_failure_ DB - PRIME DP - Unbound Medicine ER -