|Sex differences in nitrosative stress during renal ischemia.|
|PMID: 20702799 Owner: NLM Status: MEDLINE|
|Females suffer a less severe ischemic acute renal failure than males, apparently because of higher nitric oxide (NO) bioavailability and/or lower levels of oxidative stress. Because the renal ischemic injury is associated with outer medullary (OM) endothelial dysfunction, the present study evaluated sex differences in OM changes of NO and peroxynitrite levels (by differential pulse voltammetry and amperometry, respectively) during 45 min of ischemia and 60 min of reperfusion in anesthetized Sprague-Dawley rats. Endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) protein expression and their phosphorylated forms [peNOS(Ser1177) and pnNOS(Ser1417)], 3-nitrotyrosine, reduced sulfhydryl groups (-SH), and glomerular filtration rate (GFR) were also determined. No sex differences were observed in monomeric eNOS and nNOS expression, NO, or 3-nitrotyrosine levels in nonischemic kidneys, but renal -SH content was higher in females. Ischemia increased dimeric/monomeric eNOS and nNOS ratio more in females, but the dimeric phosphorylated peNOS(Ser1177) and pnNOS(Ser1417) forms rose similarly in both sexes, indicating no sex differences in nitric oxide synthase activation. However, NO levels increased more in females than in males (6,406.0 ± 742.5 and 4,058.2 ± 272.35 nmol/l respectively, P < 0.05), together with a lower increase in peroxynitrite current (5.5 ± 0.7 vs. 12.7 ± 1.5 nA, P < 0.05) and 3-nitrotyrosine concentration, (28.7 ± 3.7 vs. 48.7 ± 3.7 nmol/mg protein, P < 0.05) in females than in males and a better preserved GFR after ischemia in females than in males (689.7 ± 135.0 and 221.4 ± 52.5 μl·min(-1)·g kidney wt(-1), P < 0.01). Pretreatment with the antioxidants N-acetyl-L-cysteine or ebselen abolished sex differences in peroxynitrite, nitrotyrosine, and GFR, suggesting that a greater oxidative and nitrosative stress worsens renal damage in males.|
|Francisca Rodríguez; Susana Nieto-Cerón; Francisco J Fenoy; Bernardo López; Isabel Hernández; Raquel Rodado Martinez; Ma José González Soriano; Miguel G Salom|
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|Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-11|
|Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 299 ISSN: 1522-1490 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2010 Nov|
|Created Date: 2010-11-03 Completed Date: 2010-12-01 Revised Date: -|
Medline Journal Info:
|Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: United States|
|Languages: eng Pagination: R1387-95 Citation Subset: IM|
|Departamento de Fisiología, Facultad de Medicina, Universidad de Murcia Murcia, Spain.|
|APA/MLA Format Download EndNote Download BibTex|
Acute Kidney Injury
Antioxidants / pharmacology
Disease Models, Animal
Glomerular Filtration Rate
Kidney Medulla / drug effects, metabolism*, physiopathology
Nitric Oxide / metabolism
Nitric Oxide Synthase / metabolism
Nitric Oxide Synthase Type III / metabolism
Peroxynitrous Acid / metabolism
Reactive Nitrogen Species / metabolism*
Reperfusion Injury / complications, metabolism*, physiopathology
Sulfhydryl Compounds / metabolism
Tyrosine / analogs & derivatives, metabolism
|0/Antioxidants; 0/Reactive Nitrogen Species; 0/Sulfhydryl Compounds; 10102-43-9/Nitric Oxide; 14691-52-2/Peroxynitrous Acid; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; EC 188.8.131.52/Nitric Oxide Synthase; EC 184.108.40.206/Nitric Oxide Synthase Type III; EC 220.127.116.11/Nos1 protein, rat; EC 18.104.22.168/Nos3 protein, rat|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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