Aspirin may protect against cardiac effects of COX-2 inhibitors, say
researchers
A chemical imbalance that may be corrected with aspirin therapy, could
underlie the cardiovascular side effects of cyclo-oxygenase-2 inhibitors,
according to results from studies in mice (Cell Metabolism 2005;2:201).
The researchers explain that COX-2 inhibitors reduce the production of
prostacyclin, which keeps blood vessels open and prevents clots, without
affecting production of thromboxane, a related agent that constricts
vessels and promotes clot formation.
They studied mice that lack the prostacyclin receptor (IP) and found
that they develop salt-sensitive hypertension, cardiac hypertrophy and
severe cardiac fibrosis. They also observed that simultaneous deletion
of the thromboxane receptor (TP) does not prevent the development of
hypertension but does reduce cardiac hypertrophy and prevent fibrosis.
Lowering blood pressure in mice lacking the prostacyclin receptor also
prevented fibrosis. “Thus, elevated blood pressure is essential
for the development of cardiac injury in IP deficiency,” say the
researchers. They add that with patients taking COX-2 inhibitors, control
of hypertension could ameliorate this tendency for exaggerated end-organ
damage.
The researchers propose that blocking TP receptors, or perhaps reducing
thromboxane generation by low-dose aspirin, might protect against cardiac
end-organ damage associated with COX-2 inhibition. “However, the
practical utility of such an approach would require demonstration that
GI protection is retained,” they conclude.
Commenting (ibid, p149), Matthew Breyer, Vanderbilt University Medical
School, Nashville, Tennesse, 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 COXIBs but lack their
adverse side effects.” |
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