title: The mechanisms of the direct vascular effects of fentanyl on isolated human saphenous veins in vitro.
abstract: OBJECTIVE
  The purpose of this study was to determine the mechanism of the direct effects of fentanyl on human veins in vitro.
  
  
  METHODS
  In vitro, prospective with repeated measures.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  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).
  
  
  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.
authors.affiliation: Department of Pharmacology, Selcuk University, Akyokuş 42080, Konya, Turkey. aysesaide@hotmail.com
authors.forename: Ayşe Saide
authors.initials: AS
authors.lastname: Sahin
authors.forename: Ateş
authors.initials: A
authors.lastname: Duman
authors.forename: Esra Kismet
authors.initials: EK
authors.lastname: Atalik
authors.forename: Cemile Oztin
authors.initials: CO
authors.lastname: Ogün
authors.forename: Tahir Kemal
authors.initials: TK
authors.lastname: Sahin
authors.forename: Atilla
authors.initials: A
authors.lastname: Erol
authors.forename: Ufuk
authors.initials: U
authors.lastname: Ozergin
mesh_terms: D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005283:Fentanyl / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009292:Narcotic Antagonists / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000502:physiology; D052250:Nitric Oxide Synthase Type III; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects; D012501:Saphenous Vein / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D015220:Calcium Channels; D016861:Cyclooxygenase Inhibitors; D007004:Hypoglycemic Agents; D009292:Narcotic Antagonists; D026902:Potassium Channel Blockers; D011957:Receptors, Opioid; D012701:Serotonin; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D000254:Sodium-Potassium-Exchanging ATPase; D005283:Fentanyl