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 Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

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: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>