By EurekAlert
Thursday, November 5, 2009
AUGUSTA, Ga. – A key player in a cascade that likely
begins with stress and leads to high blood pressure and kidney
damage has been identified by researchers who say the finding may
lead to better ways to control both.
Medical College of Georgia researchers have found endothelin, a
powerful blood vessel constrictor and inflammatory peptide,
increases the number of T cells in the kidneys, which helps recruit
other immune cells, causing inflammation and destruction.
"We think that endothelin somehow causes an increase in T cells
which results in renal injury which makes the hypertension worse
and harder to control," says Dr. Karthik Krishnan, an MCG
allergy/immunology fellow who presents the findings during the 2009
American College of Allergy, Asthma & Immunology Annual Meeting
Nov. 5-9 in Miami. Dr. Krishnan was honored with one of three
Clement von Pirquet Awards for best scientific paper in
allergy/immunology presented by fellows-in-training at the
meeting.
The process likely begins in some people when stress, diet or
other factors raise levels of the hormone angiotensin II, another
powerful blood vessel constrictor, which, in turn, increases
endothelin levels. Researchers don't know why endothelin increases
T-cell levels in the kidneys. "There are still a lot of mechanistic
questions we have," notes Dr. Krishnan.
Inflammation, a part of the normal healing process, also is
increasingly identified as a major contributor to a variety of
diseases from cancer to cardiovascular disease. "We are starting to
look at inflammatory mediators or processes that make hypertension
worse with the long-term goal of finding interventions or therapies
to counteract these mediators and better control hypertension and
prevent organ damage," Dr. Krishnan says.
It's a subset of patients – with mostly uncontrolled
hypertension, likely because of a combination of environment and
genetics – that tend to have more inflammation and more
resulting kidney damage. Dr. Krishnan hopes that making the
endothelin connection will one day help identify these people
before their kidneys take a beating.
Standard urinalysis can detect protein in the urine, one of the
first signs sign that "the kidneys are falling down on the job,"
says Dr. David Pollock, renal physiologist in MCG's Vascular
Biology Center and a study co-author. "It's like a cheesecloth that
is old and worn out and the holes are getting too big." The body
should use all the protein it makes or consumes so none should show
up in urine
For the study, mice with normal blood pressures got angiotensin
II, which raised their blood pressure and the T cell count in their
kidneys. But when researchers also gave an endothelin blocker, T
cells numbers in the kidneys did not increase. To double-check the
findings, they gave angiotensin II to mice that can't make
endothelin and the T cell count stayed down, the researchers
report.
For at-risk individuals, endothelin blockers, already on the
market for pulmonary hypertension and under study for some other
conditions that result in kidney failure, may help avoid the
destruction, Dr. Pollock says.
"We're optimistic that it's important in other forms of renal
disease. It looks like this could be useful for essentially anyone
with protein in the urine. That's what's really exciting about it,"
he says.
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