Fischer M A, Schiffers P M, Struijker-Boudier H A
Department of Pharmacology and Toxicology, Cardiovascular Research Institute, Universiteit Maastricht, Netherlands.
Endocrine. 2000 Dec;13(3):393-9. doi: 10.1385/endo:13:3:393.
Renal 11beta-hydroxysteroid dehydrogenases (11beta-HSDs) are subject to modulation by various endogenous factors. 11beta-HSDs convert glucocorticoids into inactive 11-ketones and thereby determine tissue levels of active glucocorticoids and thus the extent of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation. As such, modulation of the activity of renal 11beta-HSDs may contribute to the cascade of regulatory events involved in renal electrolyte water handling. We investigated whether renal 11beta-HSDs are modulated by elevated circulating angiotensin II. In rats infused for 2 wk with angiotensin II (250 ng/[kg x min] subcutaneously), plasma angiotensin II, aldosterone, and corticosterone were raised 5.1-, 10.7-, and 2.3-fold, respectively, compared with control rats. Angiotensin II infusion raised corticosterone 11beta-oxidation 1.46- and 1.35-fold in renal cortical proximal and distal tubules (enriched by Percoll centrifugation), respectively, but had no effect on 11beta-HSD1 and 11beta-HSD2 mRNA levels (semiquantitative reverse transcriptase polymerase chain reaction), except for distal tubular 11beta-HSD1 mRNA, which was decreased to 50%. In vitro treatment of freshly isolated tubules with angiotensin II for 45 min prior to assessment of 11beta-HSD activity showed no direct acute effects of angiotensin II on tubular corticosterone 11beta-oxidation. The enhanced renal tubular corticosterone 11beta-oxidation in vivo may partly protect renal GR and MR from elevated plasma corticosterone on angiotensin II infusion.
肾11β-羟类固醇脱氢酶（11β-HSDs）受多种内源性因素调节。11β-HSDs将糖皮质激素转化为无活性的11-酮，从而决定活性糖皮质激素的组织水平，进而决定糖皮质激素受体（GR）和盐皮质激素受体（MR）的激活程度。因此，肾11β-HSDs活性的调节可能参与了肾电解质水代谢的一系列调节事件。我们研究了循环中血管紧张素II升高是否会调节肾11β-HSDs。与对照大鼠相比，给大鼠皮下注射血管紧张素II（250 ng/[kg×min]）2周后，血浆血管紧张素II、醛固酮和皮质酮分别升高了5.1倍、10.7倍和2.3倍。血管紧张素II输注分别使肾皮质近端和远端小管（通过Percoll离心富集）中的皮质酮11β氧化增加了1.46倍和1.35倍，但对11β-HSD1和11β-HSD2 mRNA水平（半定量逆转录聚合酶链反应）没有影响，除了远端小管11β-HSD1 mRNA降低至50%。在评估11β-HSD活性之前，用血管紧张素II对新鲜分离的小管进行45分钟的体外处理，结果显示血管紧张素II对小管皮质酮11β氧化没有直接的急性影响。体内肾小管皮质酮11β氧化增强可能部分保护肾GR和MR免受血管紧张素II输注时血浆皮质酮升高的影响。
