Chemical imbalance may explain painkiller's cardiac danger

September 13, 2005

The increased rate of cardiovascular complications in patients taking the cox-2 inhibitor painkiller rofecoxib (Vioxx) may result from a chemical imbalance, according to an animal study in the September Cell Metabolism. The findings suggest that low-dose aspirin might prevent the cardiac damage of such drugs and might also lead to the development of new anti-inflammatory drugs without the adverse side effects, the researchers said.

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

The new study by researchers at Duke University and Durham VA Medical Centers found that, in 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 absence of prostacyclin 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 study author Thomas Coffman.

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

Cox-2 inhibitors and other nonsteroidal, anti-inflammatory drugs (NSAIDs)--including aspirin and ibuprofen--all reduce inflammation and pain by blocking the function of cyclo-oxygenases, also known as cox enzymes. The cox enzymes, cox-1 and cox-2, normally produce prostanoids--a family of related 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. The cox-1 and cox-2 enzymes, respectively, also produce thromboxane and prostacyclin.

Traditional NSAIDs relieve pain and inflammation by simultaneously blocking the function of both cox enzymes, Coffman explained. In contrast, rofecoxib and other cox-2 inhibitors selectively limit cox-2, thereby avoiding the gastrointestinal complications of over-the-counter NSAIDs.

A 2004 study, however, found an early rise in blood pressure and an increased rate of heart attack and stroke in patients treated with rofecoxib for more than 18 months. Last year, the manufacturer withdrew the drug from the market.

The current findings may lead to new drugs that avoid the pitfalls of both traditional NSAIDs and existing cox-2 inhibitors, the researchers said.

"Ultimately, through the dissection of these intricate pathways, it may be possible to identify drugs that provide all the therapeutic effects of NSAIDs and cox-2-selective inhibitors but lack their adverse side effects," added Matthew Breyer of Vanderbilt University Medical School in an accompanying preview. "Until that time, one can only marvel at the combination of therapeutic and cardioprotective effects of nature's own compound, salicylate, and its chemically modified derivative, aspirin."
-end-
The researchers include Helene Francois, Krairerk Athirakul, David Howell, Rajesh Dash, Lan Mao, Howard A. Rockman, and Thomas M. Coffman of Duke University and Durham VA Medical Centers, Durham, NC; Garret A. FitzGerald of the University of Pennsylvania, Philadelphia, PA; and Hyung-Suk Kim and Beverly H. Koller of the University of North Carolina, Chapel Hill, NC. This work was supported by funding from the Medical Research Service of the Veterans Administration and by National Institutes of Health (B.H.K. and T.M.C.).

Francois et al.: "Prostacyclin Protects Against Elevated Blood Pressure And Cardiac Fibrosis" Publishing in Cell Metabolism, Vol. 2, September 2005, pages 201-207. DOI 10.1016/j.cmet.2005.08.005 www.cellmetabolism.org.

Cell Press

Related Blood Pressure Articles from Brightsurf:

Children who take steroids at increased risk for diabetes, high blood pressure, blood clots
Children who take oral steroids to treat asthma or autoimmune diseases have an increased risk of diabetes, high blood pressure, and blood clots, according to Rutgers researchers.

High blood pressure treatment linked to less risk for drop in blood pressure upon standing
Treatment to lower blood pressure did not increase and may decrease the risk of extreme drops in blood pressure upon standing from a sitting position.

Changes in blood pressure control over 2 decades among US adults with high blood pressure
National survey data were used to examine how blood pressure control changed overall among U.S. adults with high blood pressure between 1999-2000 and 2017-2018 and by age, race, insurance type and access to health care.

Transient increase in blood pressure promotes some blood vessel growth
Blood vessels are the body's transportation system, carrying oxygen and nutrients to cells and whisking away waste.

Effect of reducing blood pressure medications on blood pressure control in older adults
Whether the amount of blood pressure medications taken by older adults could be reduced safely and without a significant change in short-term blood pressure control was the objective of this randomized clinical trial that included 534 adults 80 and older.

Brain blood flow sensor discovery could aid treatments for high blood pressure & dementia
A study led by researchers at UCL has discovered the mechanism that allows the brain to monitor its own blood supply, a finding in rats which may help to find new treatments for human conditions including hypertension (high blood pressure) and dementia.

Here's something that will raise your blood pressure
The apelin receptor (APJ) has been presumed to play an important role in the contraction of blood vessels involved in blood pressure regulation.

New strategy for treating high blood pressure
The key to treating blood pressure might lie in people who are 'resistant' to developing high blood pressure even when they eat high salt diets, shows new research published today in Experimental Physiology.

Arm cuff blood pressure measurements may fall short for predicting heart disease risk in some people with resistant high blood pressure
A measurement of central blood pressure in people with difficult-to-treat high blood pressure could help reduce risk of heart disease better than traditional arm cuff readings for some patients, according to preliminary research presented at the American Heart Association's Hypertension 2019 Scientific Sessions.

Heating pads may lower blood pressure in people with high blood pressure when lying down
In people with supine hypertension due to autonomic failure, a condition that increases blood pressure when lying down, overnight heat therapy significantly decreased systolic blood pressure compared to a placebo.

Read More: Blood Pressure News and Blood Pressure Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.