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Hyperactive ENaC identifies hypertensive individuals amenable to amiloride therapy
A R Carter1, Z H Zhou, D A Calhoun
1Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
American Journal of Physiology. Cell Physiology
|October 16, 2001
Summary
Refractory hypertension may stem from overactive epithelial sodium channels (ENaC). Measuring lymphocyte ENaC function via patch clamp can identify patients responsive to amiloride, a drug that normalized blood pressure in some individuals.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Electrophysiology
Background:
- Primary aldosteronism and pseudohyperaldosteronism share hallmarks of hyperactive epithelial sodium channels (ENaC) and resistant hypertension.
- Peripheral blood lymphocytes express ENaC, mirroring its function and regulation in renal principal cells.
Purpose of the Study:
- To determine if lymphocyte ENaC assessment can identify hypertensive etiologies.
- To test if amiloride inhibition of hyperactive ENaC can improve refractory hypertension.
Main Methods:
- Whole-cell patch clamp electrophysiology on peripheral blood lymphocytes.
- Assessing ENaC function and regulation in normotensive, controlled hypertensive, and refractory hypertensive individuals.
- Administering amiloride to refractory hypertensive patients with identified hyperactive ENaC.
Main Results:
- Hyperactive ENaC was exclusively found in refractory hypertensive individuals.
- Amiloride therapy normalized blood pressure in four out of nine refractory hypertensive patients.
- Patients who responded to amiloride all exhibited hyperactive ENaC, while non-responders had normal ENaC activity.
Conclusions:
- Whole-cell patch clamp of lymphocytes offers a rapid and accurate method for identifying hypertensive patients likely to benefit from amiloride therapy.
- Lymphocyte ENaC activity serves as a biomarker for predicting amiloride responsiveness in certain hypertensive conditions.