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Cyclooxygenases (COX) play a key role in the regulation of renal arterial tone, but not in glomerular function,of mouse with 5/6 nephrectomy (LB725)
Author(s) -
Zhu Bijun,
Jin Jianjun,
Zhao Zhonghua,
Zhang Zhigang,
Lu Limin,
Zhu Tongyu,
Vanhoutte Paul,
Shi Yi
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb725
Subject(s) - prostacyclin , medicine , endocrinology , cyclooxygenase , blot , kidney , western blot , renal function , acetylcholine , vasodilation , macula densa , renal artery , nephrectomy , peritubular capillaries , electrical impedance myography , immunohistochemistry , vasoconstriction , podocyte , chemistry , renin–angiotensin system , blood pressure , proteinuria , enzyme , biochemistry , gene
Objectives. Hyperfusion induces shear stress, leading to macrovascular endothelial dysfunction. However, effects of hyperfusion on glomerular endothelial cells (microvascular) remain unclear. Methods. C57/BL6 mice were randomly grouped into sham‐operated (2K), 1 kidney removal (1K) and 5/6 nephroectomy groups (5/6K‐off). Renal artery and glomerulus were collected for Western blotting, polymerase chain reaction and immunohistochemistry (IHC) assay. Results. Four weeks after the surgery, arterial blood pressure was comparable among the three groups. Compared with 2K and 1K groups, 5/6K‐off mice had significantly higher levels of renal blood flow. Consistently, relaxations to acetylcholine were blunted in renal arteries, but not in aortae, of 5/6K‐off mice. Indomethacin, a non‐selective cyclooxygenase inhibitor, reduced acetylcholine‐induced relaxation in 2K group, suggesting that prostacyclin is a vasodilator in renal arteries. Indomethacin did not affect acetylcholine‐induced relaxation in 1K mice, but improved it in 5/6K‐off mice. These results indicated that prostanoids, other than prostacyclin, are involved in vasoconstriction. Western blot and IHC experiments confirmed the upregulation of cyclooxygenase‐2 expression in the renal artery of 5/6K‐off mice. Urine protein levels were similar in the three groups, when normalized with remaining glomeruli. Glomerular filtration experiments also indicated that there were no significant increase in levels of macromolecules in 5/6K‐off group. This suggested that mouse glomeruli in 5/6K‐off group have normal function. In addition, Western blotting and IHC experiments did not detect any significant changes in cyclooxygenases expressions in glomeruli. Conclusion. This study presents some intriguing effects of cyclooxygenases in a mouse kidney hyperfusion model. Prostanoids acts as a vasoconstrictor in renal artery of 5/6K‐off mice, but produces a protective effect in 2K group. However, cyclooxygenases are not involved in glomerular function. Further experiments will focus on examining the underlying mechanisms. Grant Funding Source : National Natural Science Foundation of China 81373412