Aims: To investigate the roles of cyclooxygenases (COX) and their metabolites in C57/BL6 mice with 5/6 nephrectomy, an animal model of chronic renal failure. Main methods: C57/BL6 mice were grouped into sham-operated (2K), one kidney removal (1K) and 5/6 nephrectomy groups (5/6Nx). Renal resistive index was measured by ultrasonography. Blood, aortae, renal arteries and renal cortex were collected for measurement of kidney function, assessment of vascular responsiveness, Western blotting, immuohistochemistry and enzyme-linked immunosorbent assays. Key findings: After four weeks, acetylcholine-induced relaxations were blunted in renal arteries of 1K and 5/6Nx mice; indomethacin, a non-selective COX inhibitor, improved the response in 5/6Nx, but not in 1K renal arteries. In 5/6Nx renal arteries, but not in 1K preparations, the protein presence of endothelial nitric oxide synthase (eNOS) was decreased, while that of COX-2 and its products [prostacyclin and thromboxane A(2)] were increased. The renal resistive index was lower in 5/6Nx mice, suggesting a lower resistance in the renal microvasculature. In the renal cortex of 5/6Nx mice, eNOS protein presence was increased; while the presence of COX-2 was not detectable. The prostaglandin E-2 level was lower in the 5/6Nx cortex than in the other two groups. Significance: The early stage of renal mass removal is associated with increased renal arterial constriction and reduced microvascular resistance. The former is due to downregulation of eNOS and upregulation of COX-2, leading to an increased production of prostacyclin and thromboxane A(2). A reduced production of PGE(2) in the renal cortex is important for maintaining normal renal function. (C) 2017 Published by Elsevier Inc.
[1]Fudan Univ, Zhongshan Hosp, Biomed Res Ctr, Fenglin Rd 180, CN-200032 Shanghai, Peoples R China.
[2]Fudan Univ, Zhongshan Hosp, Dept Urol, Shanghai, Peoples R China.
[3]Shanghai Key Lab Organ Transplantat, Shanghai, Peoples R China.
[4]Fudan Univ, Fac Med, Dept Pathol, Shanghai, Peoples R China.
[5]Fudan Univ, Fac Med, Dept Physiol & Pathophysiol, Shanghai, Peoples R China.
[6]Univ Hong Kong, Li Ka Shing Fac Med, Dept Pharmacol & Pharm, State Key Lab Pharmaceut Biotechnol, Hong Kong, Hong Kong, Peoples R China.
[7]Fudan Univ, Zhongshan Hosp, Dept Obstet & Gynecol, Fenglin Rd 180, CN-200032 Shanghai, Peoples R China.
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