[Expression and role of soluble epoxide hydrolase in renal tissue of two kidneys one clip hypertension rats model].

Objective: To investigate renal expression of soluble epoxide hydrolase (sEH) in 2-kidney-1-clip rats and explore the role of sEH in renal arterial stenosis hypertensive development.

Methods: Hypertensive models were established in Sprague-Dawly rats by chronic partial occlusion of left renal artery. In the study,16 male Sprague-Dawly rats were randomized into sham operation group and 2-kidney-1-lip (2K1C) group (n=8, each group), and were observed for 40 days. Before operation and every ten days after operation, systolic blood pressure (SBP) was measured and twenty-four-hour urine was collected. At the end of the observation, the blood and kidneys were harvested. The serum Na,24-hour urine protein excretion were measured. Renin activity and angiotensin II concentrition in plasm and renal tissue were evaluated by radioimmunoassay (RIA).The expression of sEH, peroxisome proliferator-activated receptor-γ (PPARγ) in kidneys were assessed by immunohistochemistry and Western blotting. Histology was analysed after kidney sections were stained by Grocott-Gomori methenamine-silver nitrate.

Results: After surgery, the systolic blood pressure in 2K1C group gradually became higher than that in sham group. Urine protein excretion was statistically increased in 2K1C group on the 30 th and 40 th days, while serum sodium was of no significant difference from those of the two groups. Renin-angiotensin system in both clipped and nonclipped kidneys were also invoked by the 2K1C surgery. Both sEH and PPARγ were upregulated in renocortex and renomedulla in 2K1C group. The two groups were compared: in SBP,on the 10 th day, (106.70±7.71) vs.(124.04±6.79) mmHg, P<0.001,and on the 40 th day,(107.80±10.01) vs. (150.40±11.76) mmHg, P<0.001; Urine protein excretion,on the 30 th day,(206.81±37.61)vs.(292.33±20.53)mg/d, P=0.005; Serum sodium, (179.76±29.20) vs. (157.72±51.00)mmol/L, P=0.44; Renin activity[plasm(50.00±13.66) vs.(132.90± 31.22)ng/(L×h),P=0.03; clipped kidney(128.40±36.88)vs.(324.90±56.66)ng/(g×h), P=0.01; nonclipped kidney(103.00±19.87)vs.(345.10±42.68)ng/(g×h), P<0.001]; Ang II [plasm(4 810.00±1 164.00)vs. (10 470.00±1 760.00) ng/L,P=0.02, clipped kidney(735.90±154.40)vs.(2 094.00±372.20)ng/g, P=0.005, nonclipped kidney(648.10±217.90)vs.(1 774.00±206.60)ng/g, P=0.002]; the expression of sEH (sEH/β-actin) in renocortex [clipped kidney (0.33±0.08) vs. (1.73±0.12), P<0.001, nonclipped kidney (0.43±0.09)vs. (0.70± 0.05), P=0.04]; the expression of PPARγ (PPARγ/β-actin) in renocortex [clipped kidney(0.17±0.05) vs. (0.89±0.11), P=0.002, and nonclipped kidney(0.27±0.07) vs. (0.56±0.07), P=0.04]. Clipped kidney showed more severe glomerulosclerosis and tubular atrophy in 2K1C group than in sham group.

Conclusion: sEH probably plays an important role in the development of hypertension in the rat models of renovascular hypertension. The activation of PPAR-γ and RAAS by renal arterial stenosis are associated with sEH upregulation, suggesting that they might regulate sEH expression and take part in hypertensive development.