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.