THE ROLE OF NITRIC OXIDE IN OBSTRUCTIVE NEPHROPATHY
2000; Lippincott Williams & Wilkins; Volume: 163; Issue: 4 Linguagem: Inglês
10.1016/s0022-5347(05)67760-9
ISSN1527-3792
AutoresAndrew Huang, Lane S. Palmer, David B. Hom, Elsa Valderrama, Howard Trachtman,
Tópico(s)Urinary Bladder and Prostate Research
ResumoNo AccessJournal of UrologyPEDIATRIC UROLOGY1 Apr 2000THE ROLE OF NITRIC OXIDE IN OBSTRUCTIVE NEPHROPATHY ANDREW HUANG, LANE S. PALMER, DAVID HOM, ELSA VALDERRAMA, and HOWARD TRACHTMAN ANDREW HUANGANDREW HUANG More articles by this author , LANE S. PALMERLANE S. PALMER More articles by this author , DAVID HOMDAVID HOM More articles by this author , ELSA VALDERRAMAELSA VALDERRAMA More articles by this author , and HOWARD TRACHTMANHOWARD TRACHTMAN More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)67760-9AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Ureteral obstruction leads to tubulointerstitial fibrosis and loss of renal function. Nitric oxide production ameliorates fibrosis due to obstructive uropathy. However, nitric oxide is produced by 3 isoforms of the enzyme, nitric oxide synthase. We evaluated the role of inducible nitric oxide synthase in obstructive uropathy using nitric oxide synthase knockout mice, and determined whether the administration of L-arginine to promote nitric oxide synthesis by alternative nitric oxide synthase isoforms modulates renal fibrosis in these animals. Materials and Methods: Complete unilateral ureteral obstruction was created in wild-type C57 and inducible nitric oxide synthase knockout mice. Control animals of each strain underwent sham surgery. Throughout the experiment mice had free access to untreated tap water or water supplemented with 10 gm./l. L-arginine. Animals were sacrificed 1 and 2 weeks, respectively, after creation of unilateral ureteral obstruction. We obtained serum as well as bladder and obstructed renal pelvic urine, and determined the nitrite level in each fluid. Renal cortical thickness was measured in the normal and obstructed kidneys. The degree of tubulointerstitial fibrosis was evaluated by trichrome staining and type I collagen deposition in kidney tissue specimens. Results: Nitrite was significantly decreased in the serum, bladder and renal pelvic urine of inducible nitric oxide synthase knockout mice with unilateral ureteral obstruction compared with that in wild-type C57 mice at 1 and 2 weeks (p <0.05). In knockout mice with unilateral ureteral obstruction 1 week in duration that drank tap or L-arginine supplemented water nitrite in serum and each urine sample was higher than in sham operated knockout controls. The level returned to baseline after 2 weeks of obstruction (p <0.05). After 2 weeks of obstruction there was significantly greater cortical thinning in knockout than in C57 mice (p <0.05). Moreover, knockout mice given L-arginine supplemented water for 2 weeks had even greater cortical thinning than after 1 week or than mice given tap water for 1 to 2 weeks (p <0.05). Decreased renal cortical thickness in knockout mice after 2 weeks of obstruction was associated with less intense trichrome staining and a virtual absence of type I collagen deposition compared with findings in the wild-type C57 strain. Conclusions: Inducible nitric oxide synthase knockout mice with unilateral ureteral obstruction have significantly lower nitrite in serum and urine than wild-type C57 mice. Knockout mice also have more severe renal cortical thinning than C57 animals after creation of unilateral ureteral obstruction. Providing L-arginine supplemented water to inducible nitric oxide synthase knockout mice exacerbates the loss of cortical thickness. Alterations in cortical thinning that we observed in knockout mice were associated with decreased tubulointerstitial fibrosis and a decreased net renal extracellular matrix accumulation. 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Google Scholar From the Divisions of Pediatric Urology, Pathology and Nephrology, Schneider Children’s Hospital, Long Island Jewish Medical Center, New Hyde Park, New York© 2000 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byTRACHTMAN H, WEISER A, VALDERRAMA E, MORGADO M and PALMER L (2018) PREVENTION OF RENAL FIBROSIS BY SPIRONOLACTONE IN MICE WITH COMPLETE UNILATERAL URETERAL OBSTRUCTIONJournal of Urology, VOL. 172, NO. 4 Part 2, (1590-1594), Online publication date: 1-Oct-2004.Chang B, Mathew R, Palmer L, Valderrama E and Trachtman H (2018) Nitric Oxide in Obstructive Uropathy: Role of Endothelial Nitric Oxide SynthaseJournal of Urology, VOL. 168, NO. 4 Part 2, (1801-1804), Online publication date: 1-Oct-2002.RAWASHDEH Y, DJURHUUS J, MORTENSEN J, HØRLYCK A and FROKIAER J (2018) THE INTRARENAL RESISTIVE INDEX AS A PATHOPHYSIOLOGICAL MARKER OF OBSTRUCTIVE UROPATHYJournal of Urology, VOL. 165, NO. 5, (1397-1404), Online publication date: 1-May-2001. Volume 163Issue 4April 2000Page: 1276-1281 Advertisement Copyright & Permissions© 2000 by American Urological Association, Inc.Keywordsnitric oxideureteral obstructionkidneyMetricsAuthor Information ANDREW HUANG More articles by this author LANE S. PALMER More articles by this author DAVID HOM More articles by this author ELSA VALDERRAMA More articles by this author HOWARD TRACHTMAN More articles by this author Expand All Advertisement PDF downloadLoading ...
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