CONTACT: DAVE PEDERSEN
2130 Medical Laboratories
Iowa City IA 52242
(319) 335-8032; fax (319) 335-8034
Release: Release: Immediate
Jan. 3, 2000
UI study looks at cellular mechanism involved in hypertension
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
University of Iowa Health Care describes the partnership between the
UI College of Medicine and the UI Hospitals and Clinics and the patient care,
medical education and research programs and services they provide.