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Comparative effect of ibuprofen on endothelial and platelet prostaglandin synthesis
Abstract:
Ibuprofen (Motrin) decreases infarct size in animal models of myocardial infarction. Inasmuch as this effect might be related to the inhibitory effect of ibuprofen on platelet function, we have evaluated its effect on platelet and endothelial prostaglandin synthesis. Human umbilical vein endothelial cultures and washed human platelets were studied. Thromboxane (TX)A2 was determined by radioimmunoassay for its stable and product TXB2 and prostacyclin was determined by radioimmunoassay for its stable end product 6-keto-prostaglandin F1 alpha. At all concentrations of ibuprofen tested, platelet TXA2 and endothelial prostacyclin synthesis were inhibited to a similar degree. Unlike aspirin, the effect of ibuprofen on prostaglandin synthesis was rapidly reversible in both endothelial and platelet systems after removal of the drug. Ibuprofen was also shown to interfere with the irreversible inhibitory effect of aspirin, suggesting that ibuprofen and aspirin might compete for binding by the cyclooxygenase. Inhibition of endothelial and platelet prostaglandin synthesis was nearly complete with 100 microM concentrations of aspirin (100%) and ibuprofen (99%). Thrombin-stimulated platelet adherence to endothelial monolayers was related inversely to the amount of prostacyclin produced by the endothelium. Adherence was maximal at concentrations (100 microM) of ibuprofen and aspirin producing near complete inhibition of prostaglandin synthesis. Maximal adherence with both drugs was comparable (28 vs. 31%). Ibuprofen showed no preferential inhibitory effect on TXA2 synthesis and, at a 100 microM concentration, was as effective as aspirin in the systems studied.
Insights
Ibuprofen, like aspirin, inhibits prostaglandin synthesis in platelets and endothelial cells. Unlike aspirin, ibuprofen's effects are reversible, suggesting potential competition for cyclooxygenase binding.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Biochemistry
Background:
- Ibuprofen reduces infarct size in myocardial infarction models.
- This effect may stem from ibuprofen's inhibition of platelet function.
Purpose of the Study:
- To evaluate ibuprofen's effect on platelet and endothelial prostaglandin synthesis.
- To compare ibuprofen's mechanism with aspirin's.
Main Methods:
- Studied human umbilical vein endothelial cells and washed human platelets.
- Measured thromboxane A2 (TXA2) and prostacyclin synthesis using radioimmunoassays.
- Assessed thrombin-stimulated platelet adherence to endothelial monolayers.
Main Results:
- Ibuprofen inhibited both platelet TXA2 and endothelial prostacyclin synthesis similarly across tested concentrations.
- Ibuprofen's inhibitory effects were rapidly reversible upon drug removal, unlike aspirin.
- Ibuprofen interfered with aspirin's irreversible inhibition, suggesting cyclooxygenase competition.
- Near-complete inhibition of prostaglandin synthesis was observed with 100 μM ibuprofen (99%) and aspirin (100%).
- Platelet adherence to endothelium was maximal with both drugs at 100 μM, inversely related to prostacyclin production.
Conclusions:
- Ibuprofen inhibits platelet and endothelial prostaglandin synthesis comparably to aspirin.
- Ibuprofen's reversible inhibition and interference with aspirin suggest cyclooxygenase competition.
- Ibuprofen's effects on prostaglandin synthesis and platelet adherence are similar to aspirin's at equivalent concentrations.