The research team of Professor Emeritus Toshiro Fujita and Research Fellow Kohei Ueda (Clinical Epigenetics Course) of the Research Center for Advanced Science and Technology, the University of Tokyo, said on June 6 that salt-sensitive hypertension develops from pure kidney dysfunction. Announced that it proved for the first time.
Hypertension is a strong risk factor for cardiovascular disease affecting 3000 million people in Japan.The effectiveness of salt-reducing therapy to reduce salt intake is widely known, suggesting that so-called salt sensitivity, which causes hypertension by excessive salt intake, is an important pathogenic mechanism.In healthy people, excessively ingested salt is excreted from the kidneys via urine to maintain normal blood pressure, so kidney dysfunction is necessary to develop salt-sensitive hypertension. The hypothesis (kidney theory) has been known for a long time.
This kidney theory has gained some support.However, it was found that gene mutations that are thought to cause such renal abnormalities and cause hypertension also cause various abnormalities in organs other than the kidney, such as blood vessels and the brain, and the kidney as the pathogenic mechanism of salt-sensitive hypertension. Recently, a "non-kidney theory" has been raised that questions the importance of.
To analyze the role of the kidney in the pathogenesis of salt-sensitive hypertension, the researchers created knockout mice in which the Hsd11b2 gene, which suppresses salt reabsorption in the kidney, is deficient only in kidney cells.The mice then developed salt-sensitive hypertension.In addition, this mouse developed hypokalemia similar to a patient with a loss-of-function mutation in the Hsd11b2 gene (Apparent Mineralocorticoid Excess; AME syndrome).When this hypokalemia was treated with a high-potassium diet, blood pressure was normalized, indicating that hypokalemia is an important onset factor of hypertension.
In addition, this mouse causes hypokalemia through activation of the epithelial sodium channel (ENaC) in the kidney, and sodium chloride cotransporter (NCC) activity in the kidney due to hypokalemia. Details of the pathogenic mechanism were also identified, such as the importance of the onset of hypokalemia in the onset of hypertension.These results not only show that renal Hsd11b2 gene abnormality is important in the pathogenic mechanism of AME syndrome, but also pure renal dysfunction, which was only a conceptual existence in the classical renal theory. It is said that it was proved that salt-sensitive hypertension develops.
Paper information:[Hypertension] Renal Dysfunction Induced by Kidney-Specific Gene Deletion of Hsd11b2 as a Primary Cause of Salt-Dependent Hypertension
