Differential effects of COX‐2 inhibitors on vascular smooth muscle cell function

Abstract

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 Ca2+ currents in rat mesenteric artery smooth muscle cells (MASMCs) was evaluated using perforated patch clamp techniques.ResultsVoltage 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 Ca2+ 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.Conclusioncoxibs display differential effects on vascular KCNQ and L‐type Ca2+ channels that may account for some off‐target cardiovascular effects. This work was supported by the AHA (0715618Z to ARM).