| Evidence for the role of reactive nitrogen species in polymicrobial sepsis-induced renal peritubular capillary dysfunction and tubular injury. | |
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MedLine Citation:
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PMID: 17494883 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Acute kidney injury (AKI) remains a frequent and serious complication of human sepsis that contributes significantly to mortality. For better understanding of the development of AKI during sepsis, the cecal ligation and puncture (CLP) murine model of sepsis was studied using intravital video microscopy (IVVM) of the kidney. IVVM with FITC-dextran was used to determine the percentage of capillaries with continuous, intermittent or no flow at 0 (sham), 10, 16, and 22 h after CLP. There was a dramatic fall in capillary perfusion as early as 10 h after CLP that persisted through 22 h. The percentage of vessels with continuous flow at 16 h decreased from 73 +/- 2% in shams to 16 +/- 2% (P < 0.05), whereas the percentage of vessels with no flow increased from 4 +/- 1% in shams to 42 +/- 2% (P < 0.05). The capillary perfusion defect preceded the rise in serum creatinine. IVVM with dihydrorhodamine-123 was used to quantify in real time reactive nitrogen species (RNS) generation by renal tubules, and the inducible nitric oxide synthase inhibitor L-iminoethyl-lysine (mg/kg) was used to examine the role of inducible nitric oxide synthase inhibitor on capillary dysfunction and RNS generation. Tubular generation of RNS was significantly elevated at 10 h after CLP and was associated with tubules that were bordered by capillaries with reduced perfusion. L-iminoethyl-lysine significantly reversed the capillary perfusion defect, blocked RNS generation, and reduced AKI. These data show that capillary dysfunction and RNS generation contribute to tubular injury and suggest that RNS should be considered a potential therapeutic target in the treatment of sepsis-induced AKI. |
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Authors:
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Liping Wu; Neriman Gokden; Philip R Mayeux |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-05-09 |
Journal Detail:
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Title: Journal of the American Society of Nephrology : JASN Volume: 18 ISSN: 1046-6673 ISO Abbreviation: J. Am. Soc. Nephrol. Publication Date: 2007 Jun |
Date Detail:
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Created Date: 2007-05-28 Completed Date: 2007-12-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9013836 Medline TA: J Am Soc Nephrol Country: United States |
Other Details:
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Languages: eng Pagination: 1807-15 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 West Markham Street #611, Little Rock, AR 72205, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acute Disease Animals Capillaries / metabolism* Cecum / injuries Disease Models, Animal Enzyme Inhibitors / pharmacology Kidney Diseases / drug therapy, metabolism*, physiopathology Kidney Tubules / blood supply, metabolism* Lysine / analogs & derivatives, pharmacology Male Mice Mice, Inbred C57BL Microscopy, Video Nitric Oxide / metabolism Nitric Oxide Synthase Type II / antagonists & inhibitors, metabolism Reactive Nitrogen Species / metabolism* Reactive Oxygen Species / metabolism Renal Circulation / physiology* Sepsis / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/N(6)-(1-iminoethyl)lysine; 0/Reactive Nitrogen Species; 0/Reactive Oxygen Species; 10102-43-9/Nitric Oxide; 56-87-1/Lysine; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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