© 1995 American Heart Association, Inc.
Articles |
Salt-Sensitive Hypertension in Transgenic Mice Overexpressing Na+-Proton Exchanger
From The Third Department of Internal Medicine (M.K., Y.H., R.N., Y.Y.) and the Department of Laboratory Medicine (S.T.), Faculty of Medicine, University of Tokyo; the Departments of Molecular Genetics (M.K., Y.N.) and Animal Models for Human Disease (K.H., Y.H., M.H.), National Institute of Neuroscience, Tokyo; Sumitomo Pharmaceuticals Research Center (T.N., Y.F., A.M.), Osaka; and the Diagnostic Division (H.K.), Immunology Laboratory, Yamasa Shoyu Co, Chiba, Japan.
Correspondence to Makoto Kuro-o, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187, Japan.
Abstract Essential hypertension is one of the most common diseases that exacerbate the risk of cardiovascular or cerebrovascular attacks. Although the etiology of essential hypertension remains unclear, recent investigations have revealed that an enhancement of Na+-proton (Na+-H+) exchange activity is a frequently observed ion transport abnormality in hypertensive patients and animal models. To test the hypothesis that increased Na+-H+ exchange causes hypertension, we produced transgenic mice overexpressing Na+-H+ exchanger and analyzed their Na+ metabolism and blood pressure. Urinary excretion of water and Na+ was significantly decreased in transgenic mice, and systolic blood pressure was elevated after salt loading. The impaired urinary excretion of Na+ suggested that the Na+-H+ exchanger overexpressed in the renal tubules increased reabsorption of Na+, which caused a blood pressure elevation by Na+ retention after excessive salt intake. Our results demonstrate that overexpression of Na+-H+ exchanger can be a genetic factor that interacts with excessive salt intake and causes salt-sensitive blood pressure elevation.
Key Words: Na+-proton exchanger • transgenic mouse • hypertension • overexpression
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