Mechanism of hypertension in metabolic syndrome: the role of central sympathoexcitation

2015 Fiscal Year Final Research Report

• Project/Area Number: 24591226
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Fujita Megumi 東京大学, 医学部附属病院, 助教 (50447405)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 高血圧 / メタボリックシンドローム / 交感神経活動 / ミネラロコルチコイド受容体 / 酸化ストレス

Outline of Final Research Achievements

We have shown previously that sympathoexcitation by brain oxidative stress mediates arterial pressure elevation in hypertension, and also shown that aldosterone-mineralocorticoid receptor (MR) activation mediates oxidative stress-induced cardiac and renal dysfunction. Then, we hypothesized that brain MR activation could mediate arterial pressure elevation through brain oxidative stress-induced sympathoexcitation. We used high-salt-loaded Dahl-salt-sensitive rats, high-fat-loaded-Sprague-Dawley rats and Dahl-S.Z-Lepr(fa)/Lepr(fa)). In these rats, mRNA expression of Sgk-1 and PAI-1 in the hypothalamus was significantly enhanced, which suggested MR activation. Moreover, chronic intracerebroventricular eplerenone significantly reduced sympathetic nerve activity and arterial pressure. In conclusion, brain aldosterone-MR activation through btsin oxidative stress-induced sympathoexcitation can be a possible pathogenic background of hypertension in metabolic syndrome.

Free Research Field

腎　高血圧