Exploration of gluco- and mineralocorticoid-dependent sodium transporter system involved in salt sensitive hypertension

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15494
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Endocrinology
• Research Institution: The University of Tokyo
• Principal Investigator: Fujita Toshiro 東京大学, 先端科学技術研究センター, 特任研究員 (10114125)
• Co-Investigator(Kenkyū-buntansha): 鮎澤 信宏 東京大学, 先端科学技術研究センター, 特任研究員 (50459517) ; 丸茂 丈史 東京大学, 医学部附属病院, その他 (70265817)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 食塩感受性高血圧 / ミネラルコルチコイド

Outline of Final Research Achievements

Pendrin is expressed in intercalated cells of the renal tubules and plays a pivotal role in maintenance of body fluid and blood pressure. The present study revealed the essential role of aldosterone-mineralocorticoid　receptor (MR)　pathway　in　the　activation　of　pendrin　by　angiotensin　II using adrenalectomy model and MR knockout mice, paving the way to the development of new therapy against salt-sensitive hypertension.
Apparent mineralocorticoid excess (APE) is caused by mutations in the HSD11B2 gene, which lead to hypertension. To delineate the role of the kidney, we generated mice with kidney-specific deletion of HSD11B2. These mice developed hypertension, along with activation of epithelial sodium channel-Na+-Cl- cotransporter activation. Mineralocorticoid receptor antagonist decreased blood pressure of the knockout mice. These results suggest the importance of 11beta HSD2 expressed in the kidney in MR activation and development of hypertension in APE syndrome.

Free Research Field

腎臓内分泌内科