Subtotal nephrectomy stimulates cyclooxygenase 2 expression and prostacyclin synthesis in the rat remnant kidney.
BACKGROUND
Recently, two isoforms of cyclooxygenase (COX) have been identified, a constitutive form (COX-1) and a mitogen-inducible form (COX-2). Several studies have suggested that COX is activated in renal insufficiency, but little is known about the relationship between progression of renal insufficiency and the COX isoforms.


METHODS
Five-sixths-nephrectomized (NX) rats were used. 4, 8, and 12 weeks after nephrectomy, the renal cortical prostaglandin contents and the expression levels of the two isoforms of COX were determined by enzyme immunoassay and Western-blotting, respectively. The localization of COX was examined by immunohistochemistry.


RESULTS
Renal cortical prostacyclin (PGI2) and COX-2 were significantly upregulated 8 and 12 weeks after NX, while COX-1 remained at the basal level. There was a high correlation between COX-2 and creatinine clearance (r = -0.845). There was also a high correlation between COX-2 and PGI2 (r = 0.816). Immunohistochemistry revealed the expression of COX-2 to be enhanced in the macula densa in NX rats.


CONCLUSIONS
Renal cortical COX-2 and prostacyclin were upregulated corresponding to the progression of renal insufficiency in NX rats. These results suggest enhancement of COX-2 expression in the macula densa, perhaps stimulated by a decrease in renal blood flow which upregulates PGI2 synthesis to protect the kidney from ischemia in renal insufficiency.
Horiba
Naoshi
N
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan. horibanos@chugai-pharm.co.jp
Kumano
Eiichi
E
Watanabe
Takeshi
T
Shinkura
Hirofumi
H
Sugimoto
Tetsuro
T
Inoue
Makoto
M
D000818:Animals; D001806:Blood Urea Nitrogen; D015153:Blotting, Western; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D018450:Disease Progression; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D007668:Kidney / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D007672:Kidney Cortex / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000201:enzymology*; D008565:Membrane Proteins; D009392:Nephrectomy; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000502:physiology
D007527:Isoenzymes; D008565:Membrane Proteins; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat