Rong Rong, Hu Gaizun, Wang Wanting, Muroya Yoshikazu, Miura Takahiro, Ogawa Yoshiko, Kohzuki Masahiro, Ito Osamu
School of Rehabilitation Medicine, NanJing Medical University, NanJing, 210000, China; Department of Rehabilitation, The First Affiliated Hospital of Nanjing Medical University, NanJing, 210000, China.
Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan.
Prostaglandins Other Lipid Mediat. 2018 Nov;139:80-86. doi: 10.1016/j.prostaglandins.2018.09.003. Epub 2018 Sep 15.
Angiotensin II (AngII) stimulates the renal production and release of 20-hydroxyeicosatetraenoic acids (20-HETE), which is a major metabolite of arachidonic acid catalyzed by CYP4A isoforms. However, the effects of AngII on CYP4A isoform expression in the kidney and its mechanism remains unclear. To clarify the regulation of CYP4A isoform expression by AngII, we examined the chronic effects of AngII and AngII type 1 receptor (AT1-R) blockade on CYP4A isoform expression. Sprague-Dawley rats were infused with vehicle or AngII for 1 week, and the AngII-infused rats were also treated with or without the AT1-R blocker, candesartan. AngII increased CYP4A isoform protein expression in the renal cortex (CO) and outer medulla (OM) in a dose-dependent manner, and candesartan inhibited the AngII-increased CYP4A expression in a dose-dependent manner. AngII increased the CYP4A isoform mRNA expression in the CO and OM, and candesartan inhibited AngII-increased CYP4A isoform mRNA expression. These results indicated that AngII chronically increased the CYP4A isoform expression in the rat kidney. The AngII-induced CYP4A isoform expression was mediated by AT1-R.
血管紧张素II（AngII）刺激肾脏生成并释放20-羟基二十碳四烯酸（20-HETE），20-HETE是由细胞色素P450 4A（CYP4A）亚型催化的花生四烯酸的主要代谢产物。然而，AngII对肾脏中CYP4A亚型表达的影响及其机制仍不清楚。为了阐明AngII对CYP4A亚型表达的调控，我们研究了AngII和血管紧张素II 1型受体（AT1-R）阻断剂对CYP4A亚型表达的长期影响。将Sprague-Dawley大鼠分为两组，一组注射溶媒，另一组注射AngII，持续1周，对注射AngII的大鼠再分别给予或不给予AT1-R阻断剂坎地沙坦进行治疗。AngII以剂量依赖性方式增加肾皮质（CO）和外髓质（OM）中CYP4A亚型蛋白的表达，坎地沙坦以剂量依赖性方式抑制AngII诱导的CYP4A表达增加。AngII增加CO和OM中CYP4A亚型mRNA的表达，坎地沙坦抑制AngII诱导的CYP4A亚型mRNA表达增加。这些结果表明，AngII长期增加大鼠肾脏中CYP4A亚型的表达。AngII诱导的CYP4A亚型表达是由AT1-R介导的。
