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Better understanding of blood vessel constrictor needed to harness its power for patients
Date:9/18/2008

To harness endothelin-1's power to constrict blood vessels and help patients manage high blood pressure or heart failure, scientists must learn more about how endothelin functions naturally and in disease states, says a Medical College of Georgia researcher.

Despite strong laboratory evidence that blocking endothelin-1 receptors would be an effective, targeted therapy for these two major health problems, the drugs failed patients, says Dr. Adviye Ergul, physiologist in the MCG Schools of Medicine and Graduate Studies.

"These endothelin-1 receptors are logical targets for drugs to treat hypertension because of their key role in vasoconstriction, but the targets are moving and we don't know how one target plays off another," says Dr. Ergul, who discussed novel aspects of endothelin receptor interaction during the 62nd High Blood Pressure Research Conference and Workshop in Atlanta.

"The current thinking in pharmacology is one hormone, one receptor equals boom: the effect. I think cells are much smarter," she says. This week, Dr. Ergul challenged colleagues across the country to consider emerging evidence that usual receptor communication is likely more complex than they thought and that disease may significantly alter communication.

Endothelin-1 receptors are known to interact: one way blood vessels keep a healthy tone, for example, is that a and b receptors on smooth muscle cells prompt constriction while b receptors on the lining of blood vessels work with nitric oxide to promote relaxation. Endothelin-1 receptors on the kidneys are a player as well, helping wring out excess water and salt. "There is a delicate balance," says Dr. Ergul.

But there's apparently more to the relationships. She holds up a handful of recent journal articles which reflect mounting evidence that receptors actively work as teams of two or more. That teamwork could change their function. New technology enables scientists t
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert  

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