The mechanisms of the direct vascular effects of fentanyl on isolated human saphenous veins in vitro. 2005

Ayşe Saide Sahin, and Ateş Duman, and Esra Kismet Atalik, and Cemile Oztin Ogün, and Tahir Kemal Sahin, and Atilla Erol, and Ufuk Ozergin
Department of Pharmacology, Selcuk University, Akyokuş 42080, Konya, Turkey. aysesaide@hotmail.com

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.

UI MeSH Term Description Entries
D007004 Hypoglycemic Agents Substances which lower blood glucose levels. Antidiabetic,Antidiabetic Agent,Antidiabetic Drug,Antidiabetics,Antihyperglycemic,Antihyperglycemic Agent,Hypoglycemic,Hypoglycemic Agent,Hypoglycemic Drug,Antidiabetic Agents,Antidiabetic Drugs,Antihyperglycemic Agents,Antihyperglycemics,Hypoglycemic Drugs,Hypoglycemic Effect,Hypoglycemic Effects,Hypoglycemics,Agent, Antidiabetic,Agent, Antihyperglycemic,Agent, Hypoglycemic,Agents, Antidiabetic,Agents, Antihyperglycemic,Agents, Hypoglycemic,Drug, Antidiabetic,Drug, Hypoglycemic,Drugs, Antidiabetic,Drugs, Hypoglycemic,Effect, Hypoglycemic,Effects, Hypoglycemic
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009126 Muscle Relaxation That phase of a muscle twitch during which a muscle returns to a resting position. Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D009292 Narcotic Antagonists Agents inhibiting the effect of narcotics on the central nervous system. Competitive Opioid Antagonist,Narcotic Antagonist,Opioid Antagonist,Opioid Antagonists,Opioid Receptor Antagonist,Opioid Reversal Agent,Competitive Opioid Antagonists,Opioid Receptor Antagonists,Opioid Reversal Agents,Agent, Opioid Reversal,Agents, Opioid Reversal,Antagonist, Competitive Opioid,Antagonist, Narcotic,Antagonist, Opioid,Antagonist, Opioid Receptor,Antagonists, Competitive Opioid,Antagonists, Narcotic,Antagonists, Opioid,Antagonists, Opioid Receptor,Opioid Antagonist, Competitive,Opioid Antagonists, Competitive,Receptor Antagonist, Opioid,Receptor Antagonists, Opioid,Reversal Agent, Opioid,Reversal Agents, Opioid
D011957 Receptors, Opioid Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known. Endorphin Receptors,Enkephalin Receptors,Narcotic Receptors,Opioid Receptors,Receptors, Endorphin,Receptors, Enkephalin,Receptors, Narcotic,Receptors, Opiate,Endorphin Receptor,Enkephalin Receptor,Normorphine Receptors,Opiate Receptor,Opiate Receptors,Opioid Receptor,Receptors, Normorphine,Receptors, beta-Endorphin,beta-Endorphin Receptor,Receptor, Endorphin,Receptor, Enkephalin,Receptor, Opiate,Receptor, Opioid,Receptor, beta-Endorphin,Receptors, beta Endorphin,beta Endorphin Receptor,beta-Endorphin Receptors
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D005283 Fentanyl A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078) Phentanyl,Duragesic,Durogesic,Fentanest,Fentanyl Citrate,Fentora,R-4263,Sublimaze,Transmucosal Oral Fentanyl Citrate,R 4263,R4263
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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