Originally created 01/26/01

Research focuses on hormone

Brain damage from strokes can be lessened by blocking a certain hormone that promotes excess cell growth in blood vessels, according to research at the Medical College of Georgia.

The work in stroke-prone rats could point the way toward preventing or lessening stroke damage, a serious problem in Georgia, researchers said.

MCG research scientist Anne Dorrance is zeroing in on aldosterone, which is part of a chemical pathway that can lead to the development of hypertension. Aldosterone raises blood pressure by encouraging sodium and water retention. Doctors can already prescribe a drug called an angiotensin converting enzyme inhibitor, or ACE inhibitor, to block the start of that chemical path to reduce hypertension.

But Dr. Dorrance was intrigued by research that showed less damage in patients who had heart attacks or strokes who took the drug spironolactone, which competes for aldosterone receptors on blood vessel walls and helps block its activity.

Using specially bred rats called stroke-prone, spontaneously hypertensive rat, Dr. Dorrance found she could limit the amount of brain damage the animals suffered from a stroke. She found that aldosterone increases the number of receptors for epidermal growth factor on the smooth muscle cells of the blood vessels. This causes the growth factor to have more impact on the cells and results in an abnormal increase in the cells, Dr. Dorrance said.

"Because of these cells multiplying, the structure of the blood vessel changes because the cells multiply and they start to push into the inside of the blood vessel," Dr. Dorrance said. "So they make the area for the blood (flow) much smaller."

The rats suffer from damage similar to that of an ischemic stroke, or a stroke from a blood clot. Spironolactone appears to limit the damage from those strokes, Dr. Dorrance said. Oddly, it doesn't seem to affect blood pressure in the rats, though the drug has been approved to help control high blood pressure in humans, Dr. Dorrance said.

The work is of particular importance to Georgia because it sits in the "Stroke Belt," said R. Clinton Webb, chairman of the MCG Department of Physiology, who has been collaborating on the research with Dr. Dorrance. Some of the issue might be genetic, Dr. Webb said.

"Part of that is partly environmental, but it is the genes that are responding to the environment, so it is difficult to sort out," Dr. Webb said.

And that would point to a way to possibly reduce strokes, Dr. Dorrance said.

"It could be important in people who have a family history of hypertension and stroke," Dr. Dorrance said. "This could be kind of a preventative measure."

Dr. Dorrance was awarded the Serle Young Investigator Award at the International Aldosterone Conference. She is now working to ensure the research is targeting the correct growth factor and is looking to use a more specific drug than spironolactone.

Reach Tom Corwin at (706) 823-3213.


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