Oxidative stress and lymphatic system: New therapeutic target for hypertension

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16007
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Okayama University of Science
• Principal Investigator: Mukohda Masashi 岡山理科大学, 獣医学部, 講師 (80824797)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 高血圧 / リンパ管 / 血管 / 内皮 / 活性酸素

Outline of Final Research Achievements

To lower cardiovascular disease and mortality, hypertension guidelines were recently changed in several developed countries. Since blood pressure is regulated by a complex interplay of various elements, such as the sympathetic nervous system, the endothelium and the immune system. Although the lymphatic system coordinates with the cardiovascular system, the linkage between the lymphatic system and hypertension remains unclear. In this study, we examined changes in contractile activities of lymphatic vessels using the hypertensive model rat SHR. We found that endothelium-dependent NO-mediated relaxation was decreased in thoracic ducts from SHR compared with control rat. Lymphatic vessel in SHR exhibited an increase in reactive oxygen species production with increased expression of NADPH oxidase 2. NADPH oxidase inhibitor restored the impaired endothelial dysfunction. These data support a new concept showing the relationship between lymphatic vessel and systemic blood pressure.

Free Research Field

獣医薬理学

Academic Significance and Societal Importance of the Research Achievements

高血圧症の原因として、血管内皮機能障害による弛緩反応の障害については議論されてきたが、リンパ管内皮機能の影響については未着手のままである。血管内皮機能障害にはROSの蓄積が密接に関与し、その原因因子として炎症性サイトカインやアンジオテンシンIIが知られているが、これについてもリンパ管を用いた検討はなされていない。本研究では、これまで報告のない「リンパ管機能と高血圧症」という観点から、高血圧症の病態機序を明らかとするところに、学術的意義ならびに社会的意義があると考える。