Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Aspirin might prevent Vioxx cardiac damage

14.09.2005


Low-dose aspirin might prevent the cardiovascular damage known to arise from use of the painkiller rofecoxib (Vioxx®), suggest new findings from mouse studies by Duke University Medical Center researchers. Their findings that a chemical imbalance might underlie such damage could also lead to the development of anti-inflammatory drugs without the adverse side effects, the researchers said.



The researchers reported their findings in the September 14, 2005, issue of Cell Metabolism.

Earlier studies in humans have found that cox-2 inhibitors such as rofecoxib cause a decline in prostacyclin, a chemical that normally keeps blood vessels open and prevents blood clots. That decline occurs without a change in concentration of thromboxane, a related agent that constricts vessels and promotes clot formation.


The new study found that, in a strain of mice prone to high blood pressure, an inability to respond to prostacyclin led to cardiac complications, including hypertension, enlarged hearts and severe scarring of the heart. Moreover, they showed, unrestrained action of thromboxane in the mice accentuated the intensity of cardiac damage caused by the high blood pressure.

"The current results suggest that such a chemical imbalance in patients taking selective cox-2 inhibitor painkillers may present a cardiovascular hazard -- particularly for people already predisposed to high blood pressure," said senior author of the study Thomas Coffman, M.D., chief of nephrology in the department of medicine.

Cox-2 inhibitors and other non-steroidal anti-inflammatory drugs (NSAIDS) -- including aspirin and ibuprofen -- all reduce inflammation and pain by blocking the function of the so-called cox enzymes, cox-1 and cox-2. Cox enzymes normally produce prostanoids-- a family of chemicals, including prostaglandins and thromboxanes, with many important functions throughout the body.

Prostaglandins produced by both enzymes promote inflammation, pain, and fever, while others made by cox-1 protect the stomach from the damaging effects of acid. Two important prostanoids produced by the cox-1 and cox-2 enzymes, respectively, are thromboxane and prostacyclin.

Traditional NSAIDs relieve pain and inflammation by simultaneously blocking the function of both cox enzymes, Coffman explained. However, the effects of such drugs on cox-1 can leave the stomach unprotected, causing gastrointestinal bleeding. Drugs such as rofecoxib, celecoxib (Celebrex®) and valdecoxib (Bextra®) avoid the gastrointestinal side effects by acting only on cox-2.

A 2004 study, however, found an increased rate of heart attack and stroke in patients treated with the specific cox-2 inhibitor rofecoxib for more than 18 months. The study also found that patients taking the drug showed a more immediate rise in blood pressure. The findings led Merck, the manufacturer of Vioxx, to withdraw the drug from the market last year.

While earlier research has implicated the abnormal chemical profile in the vascular disease associated with cox-2 inhibitors, its role in the development of high blood pressure remained unclear, Coffman said. Hypertension is the most common cardiovascular complication associated with cox-2 inhibition, he added.

To examine the consequences of prostacyclin decline for blood pressure and cardiac damage, the team manipulated mice such that they completely lacked the receptors that normally respond to the vessel dilator. The mice belonged to a strain particularly vulnerable to developing increased blood pressure when fed a diet high in salt.

"Hypertension is the most common cardiovascular complication associated with cox-2 inhibition, yet not everybody who takes the drugs develops high blood pressure," Coffman said. "The mice appear to have characteristics similar to the subset of patients who are prone to experience this side effect."

In the absence of the prostacyclin receptor, mice exhibited elevated blood pressure, the team reported. The animals also suffered exaggerated cardiac fibrosis and heart enlargement. Fibrosis, or scarring of the heart, can lead to arrhythmias and organ failure as the heart loses its ability to pump blood to the body’s tissues.

Mice lacking both the prostacyclin and the thromboxane receptors continue to suffer from high blood pressure, but do not develop the other cardiac complications, they found. The results reveal the adverse cardiovascular consequences of thromboxane when left unconstrained by prostacyclin, the team reported. Furthermore, the findings point to the imbalance of blood vessel agents as the culprit behind the most serious cardiac complications in the animals.

The mice represent an extreme example of what might happen in patients taking cox-2 inhibitors, Coffman said. While prostacyclin activity can be substantially reduced in patients taking the painkillers, the animals lacked this important blood component altogether, he explained.

"Our data suggests that therapies that block unrestrained thromboxane actions – for example, low doses of aspirin -- might protect against end-organ damage without affecting blood pressure in patients taking cox-2 inhibitors," Coffman said. "However, the practical utility of such an approach would depend on whether such a therapy would retain the gastrointestinal protection afforded by cox-2 inhibitors alone."

The researchers will next explore the effects of cox-2 inhibitors themselves in the salt-sensitive mice. Further study of the animals might also reveal the genetic factors that underlie the predisposition of particular individuals to develop high blood pressure and cardiac complications during therapy with cox-2 inhibitors.

Collaborators on the study include Helene Francois, Krairerk Athirakul, David Howell, Rajesh Dash, Lan Mao and Howard Rockman, of Duke; Hyung-Suk Kim and Beverly Koller of University of North Carolina, Chapel Hill; and Garret Fitzgerald of University of Pennsylvania.

Kendall Morgan | EurekAlert!
Further information:
http://www.duke.edu

More articles from Health and Medicine:

nachricht Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

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: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>