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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Sohn
Ju-Tae
JT
Department of Anesthesiology and Pain Medicine, Institute of Health Sciences, College of Medicine, Republic of Korea. jtsohn@nongae.gsnu.ac.kr
Ok
Seong-Ho
SH
Kim
Hee-Jin
HJ
Moon
Seon-Hak
SH
Shin
Il-Woo
IW
Lee
Heon-Keun
HK
Chung
Young-Kyun
YK
D000109:Acetylcholine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D000001:Calcimycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D000701:Analgesics, Opioid; D018727:Muscarinic Antagonists; D009292:Narcotic Antagonists; D011976:Receptors, Muscarinic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D009270:Naloxone; D000001:Calcimycin; D010890:Pirenzepine; D000109:Acetylcholine; D005283:Fentanyl