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Differential effects of COX‐2 inhibitors on vascular smooth muscle cell function
Author(s) -
Mackie Alexander R,
Brueggemann Lioubov I
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.579.2
Subject(s) - celecoxib , rofecoxib , electrical impedance myography , vasodilation , vascular smooth muscle , medicine , diclofenac , vasopressin , pharmacology , mesenteric arteries , cyclooxygenase , chemistry , artery , anesthesia , smooth muscle , biochemistry , enzyme
Selective cyclooxygenase‐2 inhibitors (known as coxibs) are efficacious anti‐inflammatory drugs. Despite their efficacy, reports of off‐target cardiovascular effects of coxibs led us to investigate the effects of these drugs on vascular smooth muscle ion channels. The ability of various coxibs to influence KCNQ K + and L‐type Ca 2+ currents in rat mesenteric artery smooth muscle cells (MASMCs) was evaluated using perforated patch clamp techniques. Results Voltage clamp recordings of MASMCs revealed that celecoxib (10 μM) enhanced KCNQ currents two‐fold while rofecoxib and diclofenac (both at 10 μM) were without effect. Celecoxib also decreased L‐type Ca 2+ channel maximal conductance three‐fold in MASMCs. Isolated artery pressure myography experiments revealed that celecoxib induced dose‐dependent dilation of rat mesenteric arteries (MAs) pre‐constricted with 100pM vasopressin. Endothelium‐denuded MAs also dilated in response to celecoxib, suggesting that this effect was endothelium‐independent. In separate experiments, celecoxib (20 μM) produced 97.6 ± 1.2% of dilation of MAs pre‐constricted with 100pM vasopressin, whereas rofecoxib and diclofenac (both at 20 μM) produced only 11.5 ± 2.5% and 5.8 ± 2.0% dilation respectively. Conclusion coxibs display differential effects on vascular KCNQ and L‐type Ca 2+ channels that may account for some off‐target cardiovascular effects. This work was supported by the AHA (0715618Z to ARM).