2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2006121402v1 18/6/1807    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, L. Articles by Mayeux, P. R. Search for Related Content PubMed PubMed Citation Articles by Wu, L. Articles by Mayeux, P. R.

Evidence for the Role of Reactive Nitrogen Species in Polymicrobial Sepsis-Induced Renal Peritubular Capillary Dysfunction and Tubular Injury

Liping Wu^*, Neriman Gokden and Philip R. Mayeux^*

Departments of ^* Pharmacology and Toxicology and Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas

Address correspondence to: Dr. Philip R. Mayeux, Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 West Markham Street, #611, Little Rock, AR 72205. Phone: 501-686-8895; Fax: 501-686-5521; E-mail: prmayeux{at}uams.edu

Received for publication December 26, 2006. Accepted for publication March 22, 2007.

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.

This article has been cited by other articles:

				C. Ronco, J. A. Kellum, R. Bellomo, and A. A. House Potential Interventions in Sepsis-Related Acute Kidney Injury Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(2): 531 - 544. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673