Xue Chun, Siragy Helmy M
Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.
Hypertension. 2005 Sep;46(3):584-90. doi: 10.1161/01.HYP.0000175814.18550.c0. Epub 2005 Jul 25.
CYP11B2 is the enzyme responsible for aldosterone synthesis mainly in the adrenal gland. In this study, we hypothesized that CYP11B2 gene, protein, and aldosterone are produced locally in kidney and regulated by low salt intake, angiotensin II type 1 (AT1) receptor and insulin-deficient diabetes hyperglycemia. We used real-time RT-PCR, immunohistochemistry staining, and microdialysis techniques to monitor changes in renal CYP11B2 mRNA and protein and aldosterone production in normal, adrenalectomized, or streptozotocin-induced insulin-deficient diabetic hyperglycemic rats. In normal kidney, CYP11B2 mRNA and protein were localized mainly in the renal cortex and upregulated by angiotensin II and low salt intake. The angiotensin II effect was reversed by AT1 receptor blocker valsartan. Immunohistochemistry staining demonstrated presence of CYP11B2 in glomeruli. Although aldosterone was absent in plasma of adrenalectomized rats, it was present in renal interstitium and tissue. Diabetes increased renal cortical and total kidney CYP11B2 mRNA and protein. Lowering blood glucose with insulin decreased total renal CYP11B2 mRNA and protein. Despite lack of significant changes in blood glucose, valsartan treatment caused significant reduction in renal CYP11B2 mRNA and protein. In presence of diabetes, there was an increase in CYP11B2 immunostaining in glomeruli and proximal tubules. This expression was abrogated with insulin or valsartan treatment. These results demonstrate the presence of all components of local renal aldosterone system. This system is physiologically active because it is regulated by angiotensin II and low salt intake. In insulin-deficient diabetes hyperglycemia rat model, glucose, insulin, and AT1 receptor modulate CYP11B2 expression in the kidney.
CYP11B2是主要在肾上腺负责醛固酮合成的酶。在本研究中，我们假设CYP11B2基因、蛋白质和醛固酮在肾脏局部产生，并受低盐摄入、1型血管紧张素II（AT1）受体和胰岛素缺乏型糖尿病高血糖的调节。我们使用实时逆转录聚合酶链反应（RT-PCR）、免疫组织化学染色和微透析技术，监测正常、肾上腺切除或链脲佐菌素诱导的胰岛素缺乏型糖尿病高血糖大鼠肾脏中CYP11B2 mRNA和蛋白质以及醛固酮产生的变化。在正常肾脏中，CYP11B2 mRNA和蛋白质主要定位于肾皮质，并被血管紧张素II和低盐摄入上调。血管紧张素II的作用被AT1受体阻滞剂缬沙坦逆转。免疫组织化学染色显示肾小球中存在CYP11B2。虽然肾上腺切除大鼠的血浆中不存在醛固酮，但它存在于肾间质和组织中。糖尿病增加了肾皮质和全肾的CYP11B2 mRNA和蛋白质。胰岛素降低血糖可降低全肾CYP11B2 mRNA和蛋白质。尽管血糖没有显著变化，但缬沙坦治疗导致肾CYP11B2 mRNA和蛋白质显著降低。在糖尿病存在的情况下，肾小球和近端小管中的CYP11B2免疫染色增加。胰岛素或缬沙坦治疗可消除这种表达。这些结果证明了局部肾醛固酮系统所有成分的存在。该系统具有生理活性，因为它受血管紧张素II和低盐摄入的调节。在胰岛素缺乏型糖尿病高血糖大鼠模型中，葡萄糖、胰岛素和AT1受体调节肾脏中CYP11B2的表达。
