Role of nitric oxide in renal tubular apoptosis of unilateral ureteral obstruction

A. Miyajima, J. Chen, D. P. Poppas, Jr Vaughan E.D., D. Felsen

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Background. The obstructed kidney in unilateral ureteral obstruction (UUO) is characterized by renal atrophy and tissue loss, which is mediated by renal tubular apoptosis. We sought to determine whether NO is involved in renal tubular apoptosis in vitro and in vivo. Methods. Rat renal tubular epithelial cells (NRK-52E) were subjected to mechanical stretch, and apoptosis and cell size were analyzed by flow cytometry. Furthermore, we studied UUO in mice lacking the gene for inducible nitric oxide synthase (iNOS-/-) and their wild-type littermates. Tubular apoptosis and proliferation were detected by immunostaining. NOS activity and NOS expression were assessed by a citrulline assay and Western blot, respectively. Results. Stretching-induced apoptosis in NRK-52E, which was reduced when NO was increased; conversely, stretch-induced apoptosis was increased when a NOS inhibitor was added to the cells. Stretched cells are larger and more apoptotic than unstretched cells. In UUO, the obstructed kidney of iNOS-/mice exhibited more apoptotic renal tubules than the wild-type mice through 14 days of UUO. The obstructed kidney of iNOS-/- mice at day 3 showed more proliferative tubules compared with wild type. The obstructed kidney of wild-type mice exhibited higher total NOS activity until day 7 after UUO compared with iNOS-/- mice. However, the obstructed kidney of day 14 wild-type mice exhibited significantly lower iNOS activity and protein compared with the day 0 kidney. Conclusion. These results suggest that mechanical stretch is related to renal tubular apoptosis and that NO plays a protective role in this system in UUO.

Original languageEnglish
Pages (from-to)1290-1303
Number of pages14
JournalKidney International
Volume59
Issue number4
DOIs
Publication statusPublished - 2001
Externally publishedYes

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Ureteral Obstruction
Nitric Oxide
Apoptosis
Kidney
Nitric Oxide Synthase Type II
Citrulline
Cell Size
Atrophy
Flow Cytometry

Keywords

  • Cell death
  • Hemodynamics
  • Obstructed kidney
  • Renoprotection
  • Stretching-induced apoptosis

ASJC Scopus subject areas

  • Nephrology

Cite this

Role of nitric oxide in renal tubular apoptosis of unilateral ureteral obstruction. / Miyajima, A.; Chen, J.; Poppas, D. P.; Vaughan E.D., Jr; Felsen, D.

In: Kidney International, Vol. 59, No. 4, 2001, p. 1290-1303.

Research output: Contribution to journalArticle

Miyajima, A, Chen, J, Poppas, DP, Vaughan E.D., J & Felsen, D 2001, 'Role of nitric oxide in renal tubular apoptosis of unilateral ureteral obstruction', Kidney International, vol. 59, no. 4, pp. 1290-1303. https://doi.org/10.1046/j.1523-1755.2001.0590041290.x
Miyajima, A. ; Chen, J. ; Poppas, D. P. ; Vaughan E.D., Jr ; Felsen, D. / Role of nitric oxide in renal tubular apoptosis of unilateral ureteral obstruction. In: Kidney International. 2001 ; Vol. 59, No. 4. pp. 1290-1303.
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AB - Background. The obstructed kidney in unilateral ureteral obstruction (UUO) is characterized by renal atrophy and tissue loss, which is mediated by renal tubular apoptosis. We sought to determine whether NO is involved in renal tubular apoptosis in vitro and in vivo. Methods. Rat renal tubular epithelial cells (NRK-52E) were subjected to mechanical stretch, and apoptosis and cell size were analyzed by flow cytometry. Furthermore, we studied UUO in mice lacking the gene for inducible nitric oxide synthase (iNOS-/-) and their wild-type littermates. Tubular apoptosis and proliferation were detected by immunostaining. NOS activity and NOS expression were assessed by a citrulline assay and Western blot, respectively. Results. Stretching-induced apoptosis in NRK-52E, which was reduced when NO was increased; conversely, stretch-induced apoptosis was increased when a NOS inhibitor was added to the cells. Stretched cells are larger and more apoptotic than unstretched cells. In UUO, the obstructed kidney of iNOS-/mice exhibited more apoptotic renal tubules than the wild-type mice through 14 days of UUO. The obstructed kidney of iNOS-/- mice at day 3 showed more proliferative tubules compared with wild type. The obstructed kidney of wild-type mice exhibited higher total NOS activity until day 7 after UUO compared with iNOS-/- mice. However, the obstructed kidney of day 14 wild-type mice exhibited significantly lower iNOS activity and protein compared with the day 0 kidney. Conclusion. These results suggest that mechanical stretch is related to renal tubular apoptosis and that NO plays a protective role in this system in UUO.

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