Changing chemistry helps explain estrogen threat to the heart

A piece of the topical puzzle of how estrogen goes from protecting women from heart disease to apparently increasing their risk later in life may have been found.

Medical College of Georgia researchers have found changes in blood vessel chemistry that may explain the dramatic flip-flop in estrogen's function that occurs in older women, taking it from a dilator of vessels to a potentially dangerous constrictor, says Dr. Richard White, MCG pharmacologist.

Dr. White will present the findings at the American Heart Association's Second International Conference on Women, Heart Disease and Stroke in Orlando, Fla., Feb. 16-19.

He hopes the findings will ultimately make hormone replacement therapy safer, possibly by adding to the mix compounds that enable estrogen's protective role before menopause.

Hormone replacement therapy, touted for its ability to reduce the risk of heart attack and stroke in postmenopausal women, appears to increase the risk of those conditions, according to findings of the Women's Health Initiative, a 15-year study of more than 161,000 women by the National Institute of Health's National Heart, Lung and Blood Institute.

This bad news about estrogen and the heart puzzled Drs. White and Scott A. Barman, also an MCG pharmacologist, as much as it did many physicians who had long prescribed it.

They were studying estrogen's effects on blood vessels, focusing on its impact on the smooth muscle cells that allow blood vessels to contract, thereby regulating blood pressure and blood flow. These researchers found that estrogen targets nitric oxide synthase 1, one of three versions of the enzyme that makes the powerful vasodilator, nitric oxide.

"What we were finding is that estrogen seems to be what you might call a natural nitroglycerin; nitroglycerin also works by making nitric oxide," Dr. White says.

Then they tried to block estrogen's activity by blocking nitric oxide. "What surprised the

Contact: Toni Baker
Medical College of Georgia

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