Key Molecule of Aggravation of Hypertensive Organ Damage by Large Blood Pressure Variability

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591104
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kurume University
• Principal Investigator: KAI Hisashi 久留米大学, 医学部, 准教授 (60281531)
• Co-Investigator(Kenkyū-buntansha): UCHIWA Hiroki 久留米大学, 医学部, 助教 (30624506) ; KAJIMOTO Hidemi 久留米大学, 医学部, 助教 (50349700) ; AOKI Yuji 久留米大学, 医学部, 助教 (80597419)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 血圧変動 / 高血圧 / 心肥大 / 線維化 / 炎症

Outline of Final Research Achievements

The aim of this study was to determine the key molecule of aggravation of hypertensive organ damage by large blood pressure (BP) variability. First, using a model of a combination of hypertension and large BP variability, large BP variability activated mineralocortioid receptor (MR), Rac, and PAK in medial smooth muscle of the intramyocardial arterioles. A sub-depressure dose of selective MR inhibitor, eplerenone prevented chronic inflammatory changes, cardiac hypertrophy, myocardial fibrosis, and LV systolic dysfunction. Accordingly, it was suggested that the Rac-PAK-MR system plays a role in the aggravation of the large BP variability-induced aggravation of hypertensive organ damages. Currently, further investigation using genetically engineered mice is on-going to determine the causal relation between MR system and large BP variability-induced aggravation of hypertensive organ damages.

Free Research Field

心臓病態学