Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Viagra deaths explained by new understanding of platelet clumping

10.01.2003


Incidents of heart attack and stroke, some fatal, in a small number of men taking the drug Viagra have remained a puzzle. After all, Viagra, commonly prescribed for erectile dysfunction, was originally developed to prevent these conditions -- not only by dilating blood vessels but also by stopping platelets in the blood from clumping.



In fact, the drug does just the opposite, according to researchers at the University of Illinois at Chicago College of Medicine. They found that Viagra, by elevating levels of a compound in cells called cyclic guanosine monophosphate, or cGMP, actually encourages platelets to aggregate.

The study, to be published in the Jan. 10 issue of the scientific journal Cell, amends 20 years of scientific claims that cGMP acts to prevent platelet aggregation.


While platelet aggregation helps minimize the loss of blood when injury occurs, it can also lead to clotting that blocks a blood vessel -- a life-threatening condition called thrombosis that can cause heart attack and stroke.

"Viagra, by itself, probably is not sufficient to cause a heart attack in healthy people, but our research suggests that it may present a risk for patients with preexisting conditions such as atherosclerosis," said Xiaoping Du, associate professor of pharmacology and the study’s lead author.

Du said he and his coworkers had not set out to investigate the cause of fatalities in Viagra patients when they began their research about five years ago. Rather, as a basic research scientist, he was hoping to illuminate the highly complex series of molecular steps that control platelet aggregation.

Platelets are disk-shaped cells that freely circulate in the blood. When a blood vessel is injured, the platelets form sticky surfaces, adhering to one another and to the damaged area to plug the hole.

Using recombinant DNA techniques, the researchers forced standard laboratory cells to manufacture two proteins key to platelet aggregation: one that helps the platelets clump together and stick to the surface of broken blood vessels, and another that activates the first. The genetic manipulation enabled the researchers to isolate and study the molecules that trigger these proteins.

Du focused on PKG, or cGMP-dependent protein kinase.

"It was accepted knowledge that cGMP, by stimulating PKG-catalyzed reactions in platelets, inhibits their clumping," said Du. To his astonishment, he and his colleagues found otherwise.

"When we put PKG into the recombinant cells, we found that we actually made the cells more adherent," Du said.

The results were so surprising that the researchers wondered whether there was something special about the laboratory cells that made them react differently. But tests in mouse and human platelets yielded the same results. Moreover, platelets from mice incapable of manufacturing PKG failed to aggregate as well as platelets from normal mice.

Reconciling their findings with earlier scientific evidence that cGMP inhibits platelet aggregation, the UIC researchers believe that cGMP initially causes platelets to clump to seal a wound, but later reverses to stop an excessive buildup of cells that might block a blood vessel. If a person were at risk of thrombosis -- if, for instance, a damaged blood vessel were already narrowed -- even the initial accumulation of platelets could be sufficient to cause a problem.

Since Viagra is known to work by inhibiting an enzyme that breaks down cGMP, and hence raises its level, Du and his colleagues tested the drug on platelets taken from normal donors. Alone, Viagra did not promote platelet aggregation, but it did so in the presence of a small amount of other compounds typically present when a blood vessel is damaged. In fact, Viagra caused the cells to clump at concentrations well below those achieved in patients prescribed the drug for erectile dysfunction.

An estimated 16 million men worldwide have taken Viagra. According to data in the Journal of the American Medical Association, 564 deaths were reported as of July 1999.


###
In addition to Du, other UIC researchers involved in the study were Zhenyi Li, Xiaodong Xi, Minyi Gu and Richard Ye.

The study was supported by the National Institutes of Health and the American Heart Association.

Sharon Butler | EurekAlert!
Further information:
http://www.uic.edu/

More articles from Health and Medicine:

nachricht Research reveals how diabetes in pregnancy affects baby's heart
13.12.2017 | University of California - Los Angeles Health Sciences

nachricht Routing gene therapy directly into the brain
07.12.2017 | 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: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Gecko adhesion technology moves closer to industrial uses

13.12.2017 | Information Technology

Columbia engineers create artificial graphene in a nanofabricated semiconductor structure

13.12.2017 | Physics and Astronomy

Research reveals how diabetes in pregnancy affects baby's heart

13.12.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>