Distinct role of intrarenal cyclooxygenase-1/2 in chronic unilateral renal ischemia

Hirobumi Tokuyama, Koichi Hayashi, Hiroto Matsuda, Eiji Kubota, Masanori Honda, Ken Okubo, Yuri Ozawa, Takao Saruta

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Aims: The role of cyclooxygenase (COX)-1/2-induced prostaglandins (PG) in unilateral chronic renal ischemia of anesthetized dogs was examined. Methods: Ischemic kidneys were established by reducing renal blood flow of left renal artery to 10% of baseline with an adjustable clip. After 4 weeks, changes in intrarenal contents of PGE2/PGI2 and angiotensin (Ang) II were evaluated with renal microdialysis and biopsy. Furthermore, the effect of a non-specific COX inhibitor (sulpyrine), a COX-2-specific inhibitor (NS398), and an Ang receptor antagonist (CS866) on renal function and renal PG contents were evaluated. Results: Unilateral renal artery clipping reduced renal plasma flow (RPF) in clipped (from 59 ± 2 to 17 ± 1 ml/min, n =18) and nonclipped kidneys (from 59 ± 2 to 44 ± 2 ml/min) and natriuresis. Intrarenal PGE2 increased only in clipped kidneys (from 114 ± 7 to 375 ± 25 pg/ml), whereas 6-keto-PGF1 α increased in both kidneys. Sulpyrine reduced intrarenal PG contents, and decreased RPF, GFR, and urinary sodium excretion (UNaV), whereas NS398 reduced UNaV in clipped (from 4.0 ± 0.9 to 1.7 ± 0.2 μEq/min) and nonclipped kidneys (from 5.4 ± 0.5 to 2.9 ± 0.3 μEq/min), without affecting renal hemodynamics. Intrarenal Ang II contents increased in clipped (from 0.70 ± 0.06 to 2.32 ± 0.33 pg/mg, n =18) and nonclipped kidneys (from 0.65 ± 0.06 to 2.45 ± 0.33 pg/mg, n =18), and CS866 improved renal hemodynamics and natriuresis. The elevated intrarenal Ang II content was suppressed by NS398 only in clipped kidneys. Conclusion: Unilateral renal ischemia elevates intrarenal PGE2 contents in clipped kidneys, which serves to countervail the aggravation of renal function. Furthermore, intrarenal COX isoforms may play differential roles, with COX-1 participating in modulation of renal hemodynamics, and COX-2 contributing to sodium excretion and Ang II formation.

Original languageEnglish
Pages (from-to)183-191
Number of pages9
JournalNephron
Volume92
Issue number1
DOIs
Publication statusPublished - 2002

Fingerprint

Cyclooxygenase 1
Cyclooxygenase 2
Ischemia
Kidney
Angiotensin II
Dinoprostone
Dipyrone
Prostaglandins
Renal Plasma Flow
Natriuresis
Hemodynamics
Renal Artery
Sodium
Cyclooxygenase Inhibitors
Cyclooxygenase 2 Inhibitors
Renal Circulation
Angiotensin Receptor Antagonists
Microdialysis
Epoprostenol

Keywords

  • Angiotensin II
  • Cyclooxygenase
  • Ischemic nephropathy
  • Prostaglandins

ASJC Scopus subject areas

  • Nephrology

Cite this

Tokuyama, H., Hayashi, K., Matsuda, H., Kubota, E., Honda, M., Okubo, K., ... Saruta, T. (2002). Distinct role of intrarenal cyclooxygenase-1/2 in chronic unilateral renal ischemia. Nephron, 92(1), 183-191. https://doi.org/10.1159/000064479

Distinct role of intrarenal cyclooxygenase-1/2 in chronic unilateral renal ischemia. / Tokuyama, Hirobumi; Hayashi, Koichi; Matsuda, Hiroto; Kubota, Eiji; Honda, Masanori; Okubo, Ken; Ozawa, Yuri; Saruta, Takao.

In: Nephron, Vol. 92, No. 1, 2002, p. 183-191.

Research output: Contribution to journalArticle

Tokuyama, H, Hayashi, K, Matsuda, H, Kubota, E, Honda, M, Okubo, K, Ozawa, Y & Saruta, T 2002, 'Distinct role of intrarenal cyclooxygenase-1/2 in chronic unilateral renal ischemia', Nephron, vol. 92, no. 1, pp. 183-191. https://doi.org/10.1159/000064479
Tokuyama, Hirobumi ; Hayashi, Koichi ; Matsuda, Hiroto ; Kubota, Eiji ; Honda, Masanori ; Okubo, Ken ; Ozawa, Yuri ; Saruta, Takao. / Distinct role of intrarenal cyclooxygenase-1/2 in chronic unilateral renal ischemia. In: Nephron. 2002 ; Vol. 92, No. 1. pp. 183-191.
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AU - Honda, Masanori

AU - Okubo, Ken

AU - Ozawa, Yuri

AU - Saruta, Takao

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N2 - Aims: The role of cyclooxygenase (COX)-1/2-induced prostaglandins (PG) in unilateral chronic renal ischemia of anesthetized dogs was examined. Methods: Ischemic kidneys were established by reducing renal blood flow of left renal artery to 10% of baseline with an adjustable clip. After 4 weeks, changes in intrarenal contents of PGE2/PGI2 and angiotensin (Ang) II were evaluated with renal microdialysis and biopsy. Furthermore, the effect of a non-specific COX inhibitor (sulpyrine), a COX-2-specific inhibitor (NS398), and an Ang receptor antagonist (CS866) on renal function and renal PG contents were evaluated. Results: Unilateral renal artery clipping reduced renal plasma flow (RPF) in clipped (from 59 ± 2 to 17 ± 1 ml/min, n =18) and nonclipped kidneys (from 59 ± 2 to 44 ± 2 ml/min) and natriuresis. Intrarenal PGE2 increased only in clipped kidneys (from 114 ± 7 to 375 ± 25 pg/ml), whereas 6-keto-PGF1 α increased in both kidneys. Sulpyrine reduced intrarenal PG contents, and decreased RPF, GFR, and urinary sodium excretion (UNaV), whereas NS398 reduced UNaV in clipped (from 4.0 ± 0.9 to 1.7 ± 0.2 μEq/min) and nonclipped kidneys (from 5.4 ± 0.5 to 2.9 ± 0.3 μEq/min), without affecting renal hemodynamics. Intrarenal Ang II contents increased in clipped (from 0.70 ± 0.06 to 2.32 ± 0.33 pg/mg, n =18) and nonclipped kidneys (from 0.65 ± 0.06 to 2.45 ± 0.33 pg/mg, n =18), and CS866 improved renal hemodynamics and natriuresis. The elevated intrarenal Ang II content was suppressed by NS398 only in clipped kidneys. Conclusion: Unilateral renal ischemia elevates intrarenal PGE2 contents in clipped kidneys, which serves to countervail the aggravation of renal function. Furthermore, intrarenal COX isoforms may play differential roles, with COX-1 participating in modulation of renal hemodynamics, and COX-2 contributing to sodium excretion and Ang II formation.

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