Ovariectomy enhances renal cortical expression and function of cyclooxygenase-2.

Abstract

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