Inhibitory effect of fentanyl on acetylcholine-induced relaxation in rat aorta

• Published in: Anesthesiology (Philadelphia) 2004-07, Vol.101 (1), p.89-96
• Main Authors: SOHN, Ju-Tae, OK, Seong-Ho, KIM, Hee-Jin, MOON, Seon-Hak, SHIN, Il-Woo, LEE, Heon-Keun, CHUNG, Young-Kyun
• Format: Article
• Language: English
• Subjects: Acetylcholine - antagonists & inhibitors; Acetylcholine - pharmacology; Analgesics, Opioid - pharmacology; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Aorta, Thoracic - drug effects; Biological and medical sciences; Calcimycin - pharmacology; Dose-Response Relationship, Drug; Fentanyl - pharmacology; In Vitro Techniques; Male; Medical sciences; Muscarinic Antagonists - pharmacology; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - drug effects; Naloxone - pharmacology; Narcotic Antagonists - pharmacology; Phenylephrine - pharmacology; Pirenzepine - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic - drug effects; Vasoconstrictor Agents - pharmacology; Vasodilator Agents - antagonists & inhibitors; Vasodilator Agents - pharmacology
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-200407000-00015

Previous study has shown that fentanyl attenuates acetylcholine-induced vasorelaxation. The goal of the current in vitro study was to identify the muscarinic receptor subtype that is mainly involved in the fentanyl-induced attenuation of endothelium-dependent relaxation elicited by acetylcholine. The effects of fentanyl and muscarinic receptor antagonists on the acetylcholine concentration-response curve were assessed in aortic vascular smooth muscle ring preparations precontracted with phenylephrine. In the rings pretreated independently with pirenzepine, 4-diphenylacetoxyl-N-methylpiperidine methiodide, and naloxone, acetylcholine concentration-response curves were generated in the presence and absence of fentanyl. The effect of fentanyl on the concentration-response curve for calcium ionophore A23187 was assessed. Fentanyl (0.297 x 10 0.785 x 10 m) attenuated acetylcholine-induced vasorelaxation in ring preparations with or without 10 m naloxone. Pirenzepine (10 to 10 m) and 4-diphenylacetoxyl-N-methylpiperidine methiodide (10 to 10 m) produced a parallel rightward shift in the acetylcholine concentration-response curve. The concentrations (-log M) of pirenzepine and 4-diphenylacetoxyl-N-methylpiperidine methiodide necessary to displace the concentration-response curve of an acetylcholine by twofold were estimated to be 6.886 +/- 0.070 and 9.256 +/- 0.087, respectively. Methoctramine, 10 m, did not alter the acetylcholine concentration-response curve. Fentanyl, 0.785 x 10 m, attenuated acetylcholine-induced vasorelaxation in the rings pretreated with 10 m pirenzepine but had no effect on vasorelaxation in the rings pretreated with 10 m 4-diphenylacetoxyl-N-methylpiperidine methiodide. Fentanyl, 0.785 x 10 m, did not significantly alter calcium ionophore A23187-induced vasorelaxation. These results indicate that fentanyl attenuates acetylcholine-induced vasorelaxation via an inhibitory effect at a level proximal to nitric oxide synthase activation on the pathway involving endothelial M3 muscarinic receptor activation in rat aorta.