J Jin1, Q Tang2, Z Li1, Z Zhao3, Z Zhang3, L Lu4, T Zhu2, P M Vanhoutte5, S W Leung5, R Tu6, Y Shi7. 1. Biomedical Research Centre, Zhongshan Hospital, Fudan University, China. 2. Department of Urology, Zhongshan Hospital, Fudan University, China; Shanghai Key Laboratory of Organ Transplantation, China. 3. Department of Pathology, Faculty of Medicine, Fudan University, China. 4. Department of Physiology and Pathophysiology, Faculty of Medicine, Fudan University, China. 5. State Key Laboratory of Pharmaceutical Biotechnology, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong. 6. Department of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, China. Electronic address: tu.ruiqin@zs-hospital.sh.cn. 7. Biomedical Research Centre, Zhongshan Hospital, Fudan University, China; Shanghai Key Laboratory of Organ Transplantation, China. Electronic address: shi.yi@zs-hospital.sh.cn.
Abstract
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 A2] 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 E2 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 A2. A reduced production of PGE2 in the renal cortex is important for maintaining normal renal function.
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 A2] 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 E2 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 A2. A reduced production of PGE2 in the renal cortex is important for maintaining normal renal function.
Authors: Ehécatl Miguel Ángel García Trejo; Abraham Said Arellano Buendía; Omegar Sánchez Reyes; Fernando Enrique García Arroyo; Raúl Arguello García; María Lilia Loredo Mendoza; Edilia Tapia; Laura Gabriela Sánchez Lozada; Horacio Osorio Alonso Journal: Int J Mol Sci Date: 2017-09-16 Impact factor: 5.923
Authors: Dong Zhu; Qunye Tang; Baixue Yu; Mei Meng; Wenjie Liu; Jiawei Li; Tongyu Zhu; Paul M Vanhoutte; Susan W S Leung; Yi Zhang; Yi Shi Journal: Br J Pharmacol Date: 2020-09-30 Impact factor: 8.739