IOWA CITY, Iowa -- A University of Iowa researcher has reported a key finding on a basic cellular mechanism involved in hypertension and how this plays a role in Liddle's syndrome, a rare, genetic form of the disease.
The research, published in the Jan. 1 issue of the Journal of Clinical Investigation, by Peter M. Snyder, M.D., UI assistant professor of internal medicine, centers on ion channels in cells called epithelial sodium channels (ENaC). These channels form the pathway for sodium to move across cells in the kidney, making them a critical regulator of blood pressure. Too much sodium absorption through these channels can lead to an increase in blood pressure, causing hypertension.
"It's been known that genetic mutations in ENaC cause a rare form of hypertension called Liddle's syndrome, but we thought ENaC could also be involved in more common forms of hypertension," Snyder said. "So, the basis of this study was to look at how these channels are regulated."
Previous research has shown that ENaC are regulated by a hormone called vasopressin, which is released by the brain in response to dehydration. Vasopressin signals the cell to increase production of a chemical "messenger" inside the cell called cyclic AMP (cAMP), leading to an increase in sodium absorption through ENaC. Snyder's goal was to better understand how this hormone actually performs its function, he said.
In his study using rat cells, Snyder found that vasopressin regulates ENaC by causing the channels to move to the cell surface, a process called translocation.
"Normally, most of the sodium channels are inside the cell in an intracellular pool. However, when these channels are stimulated by vasopressin and cAMP, this causes them to move to the cell surface. As a result, this increases the amount of sodium absorption in the kidneys and thus increases blood pressure."
In Liddle's syndrome, Snyder found that this cAMP regulation is defective, resulting in excessive sodium absorption in the kidney.
The next step, Snyder said, is to understand exactly how vasopressin and cAMP stimulate the movement of ENaC to the cell surface. This could help researchers identify proteins or other cell structures involved in this process and determine if abnormalities in these proteins could play a role in hypertension.
Future studies will also investigate whether the regulation of ENaC by cAMP is defective in patients with more common forms of hypertension.
Snyder's research was funded by the National Heart, Lung and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, both part of the National Institutes of Health, and the Roy J. Carver Charitable Trust.
Cite This Page: