Effects of Cyclooxygenase Inhibitors on Vascular Reactivity and Alterations of Cyclooxygenase Expression

Abstract

Background: There is controversy regarding whether COX-2 specific inhibitors are associated with elevation of blood pressure. We compared the effects of aspirin, indomethacin, and celecoxib for vascular reactivity induced by phenylephrine. We also tested the effects of indomethacin and NO donor on COX-1 and COX-2 protein expression, as well as nitrite production in culture medium of vascular smooth muscle cells. Materials and Methods: In this experiment, we used the isometric tension study for vascular reactivity. After 45 minutes of pretreatment with aspirin, indomethacin, celecoxib, and phenylephrine induced contractions were tested. COX-1 and COX-2 protein expressions were analyzed by Western blot and nitrite production by the Griess reaction. Results: Although celecoxib pretreatment caused enhanced arterial contraction, aspirin pretreatment induced more potent arterial contraction than celecoxib in the isometric tension study of rabbit femoral artery. COX-1 protein expression was unchanged by indomethacin, SNP and NOR-3; COX-2 protein expression was increased by the addition of indomethacin, SNP, and NOR-3. Especially, NOR-3, a NO donor, significantly increased COX-2 protein expression with unstimulated conditions as well as LPS stimulation. Induction of nitrite production was higher with NOR-3 treatment than SNP treatment with LPS stimulation. Conclusion: These results suggest that aspirin caused more potent vascular contraction than celecoxib and indomethacin. COX-2 expression in VSMC depended on the types of NO donor and LPS stimulation.