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Hypertension and the Gq signaling pathway
6/11/04 - 10/11/04, New Orleans, LA
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Scientific Sessions, the largest cardiovascular meeting
in the world, is being held in New Orleans Nov. 6–10.
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Defeating high blood pressure may be a matter of a
little molecular manipulation. Some drugs for hypertension, such
as so-called ACE inhibitors, block specific receptor proteins on
the cell. But researchers at Jefferson Medical College instead
have looked to a certain molecular pathway called the Gq
signaling pathway, showing that it plays an important role in
developing various models of hypertension. The work might lead
to new insights into the roots of hypertension, and eventually,
the scientists believe, novel therapies.
Andrea Eckhart, Ph.D., associate professor of
medicine at Jefferson Medical College of Thomas Jefferson
University in Philadelphia and her co-workers focused on drugs
known as alpha-adrenergic receptor blockers and angiotensin II
receptor blockers (including ACE inhibitors), which block
angiotensin over-production, and which can lead to high blood
pressure. Both of these receptors normally bind to a class of
receptors called Gq, which ultimately leads to hypertension.
"We thought that if we could somehow block all of
the receptors bound to this Gq coupled protein, then instead of
hitting each receptor individually, we could knock them all out
with a specific inhibitor," explains Dr. Eckhart, who presented
her team's results this week at the American Heart Association's
Scientific Sessions 2004 in New Orleans.
Dr. Eckhart, who is director of the Eugene Feiner
Laboratory in the Center for Translational Medicine in the
Department of Medicine at Jefferson Medical College, and her
team subsequently developed a Gq inhibitor and tested it in
various mouse models of hypertension. They looked at two
particular receptor proteins called GRK2 and GRK5, which are
both linked to high blood pressure in human and animal models.
They overexpressed the genes for GRK2 and GRK5, causing
hypertension in mice.
When they mated the GRK2 mouse with a mouse with a
genetic inhibition of Gq, the resulting offspring had lower
blood pressure. But when the researchers mated the GRK5 mouse
with a mouse with a Gq inhibition, the offspring's blood
pressure didn't change.
"This finding suggests that the overexpression of
both proteins leads to different pathways causing high blood
pressure," she says. According to Dr. Eckhart, finding the right
kind of drug for patients is difficult without knowing the
underlying causes of the high blood pressure. Because potential
contributing factors can include obesity, genetics, and other
lifestyle factors such as smoking and diet, patients often are
taking several drugs at once.
"The Gq pathway is a good molecular tool that
allows us to start looking in the laboratory at discerning
different pathways underlying high blood pressure," she says.
"It also might provide insights on developing potential
therapeutic strategies especially relevant for individuals
taking more than one drug at a time."
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American Heart Association - scientific sessions - 6/11/04 - 10/11/04, New Orleans, LA Legal Disclaimer
The materials presented here were prepared by independent authors
under the editorial supervision of The Doctors Lounge, and do not represent a
publication of the American Heart Association. These
materials and the related activity are not sanctioned by the American
Heart Association or the commercial supporter of the
conference, and do not constitute an official part of that conference.
The material presented here does not reflect the views of The Doctors
Lounge or
the companies providing unrestricted educational grants. These materials
may discuss uses and dosages for therapeutic products that have not been
approved by the United States Food and Drug Administration. A qualified
health care professional should be consulted before using any
therapeutic product discussed. All readers or continuing education
participants should verify all information and data before treating
patients or employing any therapies described in this educational
activity.
Copyright © 2004 The Doctors Lounge.
| Article reviewed by: |
Dr. Tamer Fouad, M.D.
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