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 Inselspital: Fewer CT scans needed after cerebral bleeding
20.03.2019 | Universitätsspital Bern

nachricht Building blocks for new medications: the University of Graz is seeking a technology partner
19.03.2019 | Karl-Franzens-Universität Graz

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 taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Solving the efficiency of Gram-negative bacteria

22.03.2019 | Life Sciences

Bacteria bide their time when antibiotics attack

22.03.2019 | Life Sciences

Open source software helps researchers extract key insights from huge sensor datasets

22.03.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>