ABSTRACT
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), Nomega-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 x 10(-6) , or 10(-5) mol/L) (p < 0.05 = significant). 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 < 0.05). A stepwise increase in tension was recorded with cumulative doses of Ca++ (p < 0.05). 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.
