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

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-PGF1alpha 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 microEq/min) and nonclipped kidneys (from 5.4 +/- 0.5 to 2.9 +/- 0.3 microEq/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.

• Authors: Hirobumi Tokuyama, Koichi Hayashi, Hiroto Matsuda, Eiji Kubota, Masanori Honda, Ken Okubo, Yuri Ozawa, Takao Saruta
• Journal: Nephron (Nephron) Vol. 92 Issue 1 Pg. 183-91 (Sep 2002) ISSN: 1660-8151 [Print] Switzerland
• PMID: 12187101 (Publication Type: Journal Article)
• Copyright: Copyright 2002 S. Karger AG, Basel

Chemical References

• Isoenzymes
• Angiotensin II
• 6-Ketoprostaglandin F1 alpha
• Sodium
• Cyclooxygenase 1
• Cyclooxygenase 2
• Prostaglandin-Endoperoxide Synthases
• Dinoprostone

Topics

• 6-Ketoprostaglandin F1 alpha (metabolism)
• Angiotensin II (biosynthesis)
• Animals
• Blood Pressure
• Cyclooxygenase 1
• Cyclooxygenase 2
• Dinoprostone (metabolism)
• Disease Models, Animal
• Dogs
• Glomerular Filtration Rate
• Ischemia (metabolism, physiopathology)
• Isoenzymes (metabolism)
• Kidney (enzymology)
• Kidney Failure, Chronic (metabolism, physiopathology)
• Male
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Renal Circulation
• Sodium (urine)