Inhibitory Effect of Fentanyl on Acetylcholine-induced Relaxation in Rat Aorta

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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 × 10−6, 0.785 × 10−6 m) attenuated acetylcholine-induced vasorelaxation in ring preparations with or without 10−6 m naloxone. Pirenzepine (10−7 to 10−6 m) and 4-diphenylacetoxyl-N-methylpiperidine methiodide (10−9 to 10−8 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, 10−7 m, did not alter the acetylcholine concentration–response curve. Fentanyl, 0.785 × 10−6 m, attenuated acetylcholine-induced vasorelaxation in the rings pretreated with 10−7 m pirenzepine but had no effect on vasorelaxation in the rings pretreated with 10−8 m 4-diphenylacetoxyl-N-methylpiperidine methiodide. Fentanyl, 0.785 × 10−6 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.

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