Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Estrogen receptor-a disruption and vasodilation in coronary arteries

13.11.2003


In women, the risk of coronary heart disease increases significantly after menopause. Estrogen therapy, however, reduces the risk of cardiovascular disease in healthy postmenopausal women. Estrogen enhances endothelial function of the coronary arteries, and this may contribute to the cardioprotective effects of the female hormone.



The precise mechanisms that mediate the beneficial effects of estrogen on arterial endothelial function are incompletely understood. What is known is that the long-term effects of estrogen occur through activation of estrogen receptors and subsequent modulation of gene expression. Moreover, estrogen has also been shown to effect endothelium-dependent function via its effects on expression of endothelial nitric oxide synthase.

A New Study


Accordingly, a new study tests the hypothesis that estrogen modulates nitric oxide (NO)-dependent vasodilation of coronary arteries through its action on estrogen receptor-á (ER-á) to increase protein levels of endothelial nitric oxide synthase (eNOS) and Cu/Zn superoxide dismutase (SOD-1). The authors of the study, entitled “Regulation of Nitric Oxide-Dependent Vasodilatation in Coronary Arteries of Estrogen Receptor-á-Deficient Mice,” are Judy M. Muller-Delp, Kathryn E. Nichol, Texas A&M University, College Station, TX; and Dennis B. Lubahn, Brian J. Philips, Elmer M. Price, Edward M. Curran and M. Harold Laughlin, all of the University of Missouri, Columbia, MO. Their findings appear in the November 2003 edition of the American Journal of Physiology—Heart and Circulatory Physiology, one of 14 journals published each month by the American Physiological Society (APS).

Methodology

The investigators followed the primary procedures outlined below:

Animals: A total of 43 ERá knockout (ERáKO) mice and 36 wild-type (WT) female mice were used for the study of coronary artery vasomotor reactivity experiments. A total of 19 ERáKO and 18 WT females were used for immunoblot experiments. The average age of ERáKO mice was 16 + 1 wk. In WT mice, the average age was 15 + 1 wk. Within the WT group, 16 mice were ovariectomized. Sixteen ERáKO mice were ovariectomized. Experiments were performed beginning 10 days or more after ovariectomy. Estrogen treatment was initiated after 10 days of rest following the procedure. Seventeen of the ovariectomized ERáKO and eight of the ovariectomized WT mice received subcutaneous implants of a 17â-estradiol (E2) pellet; E2 treatment was continued for 14 days before the mice died and the coronary arteries were harvested.

Isolation of coronary arteries: The hearts were excised and placed in cold saline solution. With the use of a dissecting microscope, coronary arteries were dissected free of surrounding myocardium and cannulated. Arteries that exhibited leaks were discarded and the remainder pressurized. Spontaneous tone was ensured between the WT and ERáKO mice.

Evaluation of eNOS and SOD-1 protein: Coronary arteries were isolated from the myocardium, as noted above, and frozen in microcentrifuge tubes. Because there was insufficient protein in a single mouse coronary artery to allow measurement of protein content and still have sufficient sample to run on an SDS gel, it was necessary to pool samples of coronary arteries from three mice into one sample. The eNOS and SOD-1 protein content was determined by loading equal amounts of total artery protein from equal numbers of different groups on the same gel, allowing comparisons between groups on the same gel.

Solutions and drugs: Stock solutions of albumin and endothelin were used.

Data analysis: Tone development was expressed as the percent decrease from maximal diameter according to the formula: Tone (%) = [(Dm – D8)/Dm] x 100, where Dm is the maximal diameter recorded at 60 cmH2O and Ds is the steady-state diameter recorded after equilibration of the vessel. Vasodilatory responses were recorded as actual diameters and subsequently expressed as the percent of maximal relaxation, according to the formula Relaxation (%) = [(D8 – Db)/Dm – Db)] x 100, where Ds is recorded after each addition of the drug and Db is the initial baseline diameter recorded immediately before the first addition of the vasodilatory agent. A two-way repeated-measures ANOVA was used to detect differences between and within factors. Statistical significance was defined as P < 0.05.

Results

The primary findings of this study reveal that:
  • NO-mediated vasodilation was preserved in coronary arteries from ERáKO mice;

  • SOD-1 protein content increased in coronary arteries from ERáKO mice;

  • ovariectomy reduced NO-mediated vasodilation and protein levels for eNOS and SOD-1 in ERáKO mice; and

  • E2 supplementation restored NO-mediated vasodilation and protein content of eNOS and SOD-1 in ovariectomized ERáKO mice.

Conclusions and Discussion

Based on the above findings, the researchers conclude that NO-mediated dilation is preserved in ERáKO mice through compensatory activation of ER-á independent pathways. Further study is needed to determine whether modulation of endothelium-dependent, NO-mediated vasodilation in coronary arteries occurs through an ER-â pathway.


Source: November 2003 edition of the American Journal of Physiology—Heart and Circulatory Physiology.

Donna Krupa | APS
Further information:
http://www.the-aps.org/press/journal/21.htm

More articles from Health and Medicine:

nachricht Custom-tailored strategy against glioblastomas
26.09.2016 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

Im Focus: Launch of New Industry Working Group for Process Control in Laser Material Processing

At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.

In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...

Im Focus: New laser joining technologies at ‘K 2016’ trade fair

Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.

K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

ICPE in Graz for the seventh time

20.09.2016 | Event News

Using mathematical models to understand our brain

16.09.2016 | Event News

 
Latest News

How to merge two black holes in a simple way

26.09.2016 | Physics and Astronomy

Australian technology installed on world’s largest single-dish radio telescope

26.09.2016 | Physics and Astronomy

New mechanisms uncovered explaining frost tolerance in plants

26.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>