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Arachidonate CYP hydroxylases of kidney contribute to formation of hypertension and maintenance of blood pressure.
Acta Pharmacologica Sinica ( IF 6.9 ) Pub Date : 2002-06-13
Fan Zhang 1 , Jia-Qing Qian , Dao-Wen Wang
Affiliation  

AIM To investigate the relationship of kidney-specific expression of cytochrome P-450 (CYP) 4A1 and the blood pressure. METHODS The specific sense and antisense CYP4A1 cDNA was administered respectively with the help of eukaryotic expression vector pcDNA3.1 to the Sprague-Dawley (SD) rats via sublingual vein (2 mg/kg). The systolic blood pressure of rats was assessed by the tail- cuff method, and the relative tissue expression of CYP4A1 was analyzed by Western blot and Northern blot at RNA and protein levels in the brain, heart, lung, liver, and kidney of control, sense, and anti-sense CYP4A1 cDNA-treated rats. RESULTS Two weeks after the injection of the sense and antisense CYP4A1 cDNA recombinants respectively, the mean systolic pressure of the transgenic rats increased by 1.8 kPa +/- 0.3 kPa (13.2 mmHg +/- 2.5 mmHg) or decreased by 1.7 kPa +/- 0.3 kPa (13.0 mmHg +/- 2.2 mmHg) compared with control. At the levels of transcription and translation, the Northern and Western blots all demonstrated that CYP4A1 preferentially overexpressed in the kidney. CONCLUSION The administration of sense and antisense CYP4A1 cDNA induced hypertension and hypotension, respectively, which indicated that renal arachidonate hydroxylase contributed to the formation of hypertension and maintenance of blood pressure in normotensive rats.

中文翻译:

肾脏的花生四烯酸CYP羟化酶有助于形成高血压和维持血压。

目的探讨肾脏特异性细胞色素P-450(CYP)4A1的表达与血压的关系。方法在真核表达载体pcDNA3.1的帮助下,经舌下静脉(2 mg / kg)分别对SD大鼠进行特异性有义和反义CYP4A1 cDNA的表达。用尾套法评估大鼠的收缩压,并通过Western blot和Northern blot在对照的脑,心脏,肺,肝和肾的RNA和蛋白质水平上分析CYP4A1的相对组织表达,有义和反义CYP4A1 cDNA处理的大鼠。结果分别注射有义和反义CYP4A1 cDNA重组体两周后,转基因大鼠的平均收缩压增加1.8 kPa +/- 0.3 kPa(13.2 mmHg +/- 2.5 mmHg)或降低1。与对照组相比为7 kPa +/- 0.3 kPa(13.0 mmHg +/- 2.2 mmHg)。在转录和翻译水平上,Northern和Western印迹均证明CYP4A1在肾脏中优先过表达。结论给予有义和反义CYP4A1 cDNA可分别引起高血压和低血压,这表明肾花生四烯酸羟化酶可促进血压正常大鼠的高血压形成和维持血压。
更新日期:2019-11-01
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