Ovariectomy enhances renal cortical expression and function of cyclooxygenase-2

Kidney Int. 2004 Nov;66(5):1966-76. doi: 10.1111/j.1523-1755.2004.00983.x.

Abstract

Background: Cyclooxygenase-2 (COX-2) inhibitors are used as analgesics in postmenopausal women, who develop edema and require a salt-restricted diet. This study was performed to determine the renal expression of COX-2 and on COX-2-dependent regulation of renal blood flow (RBF) in ovariectomized rats.

Methods: Sprague-Dawley rats were divided into 4 groups: sham-operated rats fed a normal-salt diet (Sh+NS) or a low-salt diet (Sh+LS), and bilaterally ovariectomized rats fed a normal-salt diet (Ox+NS) or a low-salt diet (Ox+LS) (N= 6 in each group). Estrogen replacement therapy was performed on other ovariectomized rats. A renal clearance study was performed in anesthetized animals.

Results: Ovariectomy increased renal cortical COX-2 expression independently of dietary salt intake (Sh+NS <Ox+N; Sh+LS <Ox+LS). Inhibition of COX-2 by NS398 reduced the urinary excretion of 6-keto-prostaglandin F1alpha in all 4 groups, although the reduction was greater in the Ox+LS group than in the Ox+NS and Sh+LS groups, which in turn had a greater reduction than the Sh+NS group. RBF significantly decreased in every group except the Sh+NS group, but no effect on blood pressure, inulin clearance, or urinary sodium excretion was seen. The decrease in RBF was significantly greater in the Ox+LS group than in the Sh+LS and Ox+NS group. The decrease in RBF was dependent on cortical RBF in the Sh+LS and Ox+NS groups, and on both cortical and medullary RBF in the Ox+LS group. Estrogen replacement therapy reversed the ovariectomy-induced changes.

Conclusion: Estrogen-dependent COX-2 expression plays an important role in the RBF regulation in female rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / urine
  • Animals
  • Blotting, Western
  • Cyclooxygenase 2
  • Dinoprostone / urine
  • Female
  • Immunohistochemistry
  • Kidney / metabolism
  • Kidney Cortex / enzymology*
  • Kidney Medulla / enzymology
  • Mucoproteins / metabolism
  • Ovariectomy*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Prostaglandin-Endoperoxide Synthases / physiology*
  • Prostaglandins / urine
  • Rats
  • Rats, Sprague-Dawley
  • Renal Circulation / physiology*
  • Renin / blood
  • Uromodulin

Substances

  • Mucoproteins
  • Prostaglandins
  • Uromodulin
  • 6-Ketoprostaglandin F1 alpha
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Renin
  • Dinoprostone