The mechanisms of the direct vascular effects of fentanyl on isolated human saphenous veins in vitro.

Objective: The purpose of this study was to determine the mechanism of the direct effects of fentanyl on human veins in vitro. Design: In vitro, prospective with repeated measures. Setting: University research laboratory. Interventions: Dose-response curves were obtained for cumulative doses of fentanyl (10 −9 -10 −5 mol/L) on saphenous vein strips precontracted with (10 −6 mol/L) 5-hydroxytryptamine incubated with either naloxone (10 −4 mol/L), Nω-nitroL-arginine-methyl ester (L-NAME) (10 −4 mol/L), indomethacin (10 −5 mol/L), glibenclamide (10 −4 mol/L), tetraethylammonium (10 −4 mol/L), or ouabain (10 −5 mol/L). Vein strips were also exposed to a Ca ++ -free solution and 0.1 mmol/L of ethylene glycol-bis-(b-aminoethylether) N,N′-tetraacetic acid; 5-hydroxytryptamine (10 −6 mol/L) was added to the bath before cumulative Ca ++ (10 −4 −10 −2 mol/L). The same procedure was repeated in the presence of fentanyl (10 −6 , 3 × 10 −6 , or 10 −5 mol/L) ( p Measurements and Main Results: Preincubation of vein strips with naloxone, L-NAME, or indomethacin did not influence the relaxant responses to fentanyl ( p > 0.05). Tetraethylammonium, glibenclamide, and ouabain reduced the relaxation response to fentanyl ( p ++ ( p Conclusions: The present results show that fentanyl causes vasodilatation via both endothelium- and opioid receptor-independent mechanisms in the human saphenous vein. The relaxant effects of fentanyl are probably via activation of K + channel and Na + K + -adenosine trisphosphatase and inhibition of Ca ++ channel.