blood flow in brain

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Estrogen Receptor Regulates Blood Flow in Brain

Library: MED

Keywords: ESTROGEN, BRAIN, NITRIC OXIDE, BLOOD PRESSURE, STROKE,

PROSTACYCLIN

Description: A specific receptor for the sex hormone estrogen in the

brain helps regulate pressure and blood flow there, a UC Irvine

College of Medicine research team has found. (J. of Applied

Physiology, Nov-2001)

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160-AP-01

FOR IMMEDIATE RELEASE

ESTROGEN RECEPTOR REGULATES BLOOD FLOW IN BRAIN, UC IRVINE STUDY FINDS

May Result in Ways to Prevent Stroke, Brain Injury

Irvine, Calif., Oct. 23, 2001 -- A specific receptor for the sex

hormone estrogen in the brain helps regulate pressure and blood flow

there, a UC Irvine College of Medicine research team has found.

The receptor, which appears to influence certain genes' ability to

produce nitric oxide and other chemicals that widen blood vessels, may

be an effective target for new drugs to treat stroke and other

injuries to the brain caused by high blood pressure. The researchers'

study, conducted on mice, appears in the November issue of the Journal

of Applied Physiology.

Sue Duckles, professor of pharmacology, and her colleagues found that

the receptor, called alpha-ER, regulated estrogen's ability to dilate

blood vessels in the brain by raising levels of nitric oxide and

another known dilator called prostacyclin. By raising levels of nitric

oxide and prostacyclin, estrogen could lower pressure in the brain's

arteries.

" We believe this study is among the first to show how estrogen affects

arteries in the cerebral cortex, " Duckles said. " This receptor could

help explain why women have fewer strokes than men before they reach

menopause, and this knowledge may eventually lead to new treatments

for stroke and other vascular disorders in the brain. Future research

may expand our understanding of how blood pressure is regulated

elsewhere in the body. "

Blood pressure is a major risk factor in stroke and other

cardiovascular disease. While the risk in women who have not reached

menopause is lower than men, nearly 2 million women have a stroke each

year. About 93,000 of them die of it, according to the National Heart,

Lung and Blood Institute. In addition, about 10 percent of American

women between the ages of 45 and 65 has heart disease; that proportion

rises to 25 percent of women older than 65. Of women older than 65,

about half have high blood pressure. Researchers suspect that a large

reason for this rise is the diminishing levels of estrogen in older age.

Duckles and her colleagues found that estrogen treatment for one month

resulted in elevated levels of nitric oxide synthase and

cyclooxygenase-1, enzymes responsible for manufacturing the

vasodilators, nitric oxide and prostacyclin. Mice who had been bred

without the alpha-ER receptor were less able to dilate blood vessels

when they were given estrogen. This led researchers to conclude that

it was this receptor that controlled estrogen's actions on blood

vessels in the brain.

Further, the receptor was located in the innermost layer of the blood

vessel wall, known as the endothelium. From there, it controlled the

manufacture of enzymes that produce chemicals that dilate or constrict

the vessels.\\\

" Estrogen appears to control how genes produce at least some of the

enzymes that affect dilation and pressure in vessels in the brain, "

Duckles said. " While scientists knew that an estrogen receptor was at

work, they didn't know which specific type played the most important

role. By identifying alpha-ER, we have brought this work closer to

eventually identifying possible drugs that work on the receptor to

increase blood flow. "

The researchers now are exploring other enzymes and genes that may be

controlling dilation and blood pressure and conducting more tests to

determine what chemicals may best control the alpha-estrogen receptor.

Duckles' colleagues in the study included Greg Geary, Anne Marie

McNeill, Ospina and Krause of UCI, and Korach of

the National Institute of Environmental Health Sciences in Research

Triangle Park, N.C. The National Heart, Lung and Blood Institute

supported the study.

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