Huesler Carina, Lauterburg Meret, Frey Brigitte M, Frey Felix J
Department of Nephrology, Hypertension and Clinical Pharmacology, University Hospital Berne Berne, Switzerland.
Physiol Rep. 2013 Oct;1(5):e00101. doi: 10.1002/phy2.101. Epub 2013 Oct 11.
Recently, evidence was presented that uninephrectomy induces salt-sensitive hypertension in rats. The increase in blood pressure was abrogated by a mineralocorticoid receptor antagonist but not by an aldosterone synthase inhibitor. Here, we hypothesize that mineralocorticoid receptor activation occurred by an 11beta-hydroxy-glucocorticosteroid, as a consequence of dysregulated 11beta-hydroxysteroid dehydrogenase enzymes. Therefore, 3-week-old Sprague-Dawley rats were either uninephrectomized or sham operated and given a normal (0.4%) or high (8%)-salt diet. At week 8, a telemetric device was implanted, and during week 13 blood pressure continuously measured and urine was collected. The animals were sacrificed thereafter and liver and kidney were harvested. Steroid metabolites were analyzed by GC-MS and mRNA assessed by PCR. Uninephrectomy caused a distinct salt-sensitive hypertension. The increase in blood pressure correlated significantly with a decline in the apparent activity of 11beta-hydroxysteroid dehydrogenase 2 and an increase of 11beta-hydroxysteroid dehydrogenase 1, when urinary corticosterone metabolites were considered. These results were mirrored by the corresponding metabolite ratios assessed in renal and liver tissue. Changes in enzyme activities were in part explained by changes in the mRNA content. In conclusion, mineralocorticoid receptor-dependent salt sensitivity after UNX in rats appears to be mediated by glucocorticoids.
最近，有证据表明，大鼠单侧肾切除可诱发盐敏感性高血压。盐皮质激素受体拮抗剂可消除血压升高，但醛固酮合酶抑制剂则不能。在此，我们假设盐皮质激素受体激活是由11β-羟基糖皮质激素引起的，这是11β-羟基类固醇脱氢酶失调的结果。因此，将3周龄的Sprague-Dawley大鼠进行单侧肾切除或假手术，并给予正常（0.4%）或高盐（8%）饮食。在第8周时植入遥测装置，并在第13周期间连续测量血压并收集尿液。此后处死动物，摘取肝脏和肾脏。通过气相色谱-质谱联用仪分析类固醇代谢产物，通过聚合酶链反应评估mRNA。单侧肾切除导致明显的盐敏感性高血压。当考虑尿皮质酮代谢产物时，血压升高与11β-羟基类固醇脱氢酶2的表观活性下降以及11β-羟基类固醇脱氢酶1的增加显著相关。这些结果在肾和肝组织中评估的相应代谢产物比率中得到了反映。酶活性的变化部分由mRNA含量的变化解释。总之，大鼠单侧肾切除后盐皮质激素受体依赖性盐敏感性似乎由糖皮质激素介导。
