Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Changing Chemistry Helps Explain Estrogen Threat to the Heart

17.02.2005


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 heck out of me was after we blocked nitric oxide production and added estrogen, we got a contraction,” says Dr. White. “Estrogen now had turned into a constrictor agent, an agent that would increase blood pressure.”

They looked further and found that normal aging decreases levels of the cofactors L-arginine and tetrahydrobiopterin – both critical to nitric oxide synthase’s production of nitric oxide.

Instead of making nitric oxide, estrogen was producing the powerful age-promoting – and apparently vasoconstricting – oxygen-free radical, superoxide. “At first, I thought it was an artifact,” says Dr. White, who recently received a $1.2 million, four-year grant from the NHLBI to pursue his findings. But using a porcine heart that is very similar to the human heart, he and Dr. Barman, along with Dr. David J. Fulton, a pharmacologist in the MCG Vascular Biology Center, found that every time they blocked nitric oxide production, estrogen became a vasoconstrictor.

“Under normal conditions, such as a pre-menopausal woman, this enzyme, nitric oxide synthase, makes nitric oxide,” says Dr. White. “But if you block the production of nitric oxide, this nitric oxide synthase now has a secondary product that normally isn’t made in an appreciable form. Now it makes a compound called superoxide. It’s an oxidant, and oxidation is bad in general. It causes a lot of cellular damage. But what we also have found is that now, instead of causing relaxation, it causes constriction. So you completely flip-flop the response here.

“One of the things this means is that menopause is a good thing, a sort of revolutionary endocrinology idea,” says Dr. White. “Menopause is adaptive because a woman is not supposed to have as much estrogen when she gets older because it can kill her.” He holds up a graph plotting the dramatically dropping rates of tetrahydrobiopterin over a woman’s life, a drop that parallels the drop in estrogen levels. “We have to confirm it,” he says of the new grant in which researchers will use different drugs to mimic aging, drugs that knock out L-arginine and tetrahydrobiopterin, to try to create an aged artery and restudy estrogen’s impact.

“Estrogen is so powerful; it affects every system in your body. We are looking with tunnel vision at its effect on blood pressure control. What would this do to bone? What would this do to Alzheimer’s? What happens to the brain is probably very similar,” he says as critical cofactors drop that enable estrogen to relax blood vessels. “This could be a mechanism that would affect practically every system in the body.”

Studies leading to the latest grant also were funded by the NHLBI as well as the American Heart Association.

Toni Baker | EurekAlert!
Further information:
http://www.mcg.edu

More articles from Life Sciences:

nachricht Tag it EASI – a new method for accurate protein analysis
19.06.2018 | Max-Planck-Institut für Biochemie

nachricht How to track and trace a protein: Nanosensors monitor intracellular deliveries
19.06.2018 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

Im Focus: Photoexcited graphene puzzle solved

A boost for graphene-based light detectors

Light detection and control lies at the heart of many modern device applications, such as smartphone cameras. Using graphene as a light-sensitive material for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Carbon nanotube optics provide optical-based quantum cryptography and quantum computing

19.06.2018 | Physics and Astronomy

How to track and trace a protein: Nanosensors monitor intracellular deliveries

19.06.2018 | Life Sciences

New material for splitting water

19.06.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>