Inhibitory Effect of Fentanyl on Phenylephrine-Induced Contraction of the Rat Aorta

PURPOSE: Fentanyl was reported to inhibit the α(1)-adrenoceptor agonist-induced contraction. The goal of this in vitro study was to identify the α(1)-adrenoceptor subtype primarily involved in the fentanyl-induced attenuation of phenylephrine-induced contraction in isolated endothelium-denuded rat aorta. MATERIALS AND METHODS: Aortic rings were suspended in order to record isometric tension. Concentration-response curves for phenylephrine (10(-9) to 10(-5) M) were generated in the presence or absence of one of the following drugs: fentanyl (3×10(-7), 10(-6), 3×10(-6) M), 5-methylurapidil (3×10(-8), 10(-7), 3×10(-7) M), chloroethylclonidine (10(-5) M) and BMY 7378 (3×10(-9), 10(-8), 3×10(-8) M). Phenylephrine concentration-response curves were generated in the presence or absence of fentanyl in rings pretreated with either 3×10(-9) M prazosin, 10(-9) M 5-methylurapidil or 3×10(-9) M BMY 7378. RESULTS: Fentanyl (10(-6), 3×10(-6) M) attenuated phenylephrine-induced contraction in the rat aorta. 5-Methylurapidil and BMY 7378 produced a parallel rightward shift in the phenylephrine concentration-response curve. The pA(2) values for 5-methylurapidil and BMY 7378 were estimated to be 7.71 ± 0.15 and 8.99 ± 0.24, respectively. Fentanyl (10(-6) M) attenuated phenylephrine-induced contraction in rings pretreated with 10(-9) M 5-methylurapidil, but did not alter the rings when pretreated with 3×10(-9) M BMY 7378. Pretreatment of the rings with chloroethylclonidine showed a 72.9 ± 2.3% reduction in phenylephrine-induced maximal contraction. CONCLUSION: The results suggest that fentanyl attenuates phenylephrine-induced contraction by inhibiting the pathway involved in the α(1D)-adrenoceptor-mediated contraction of the rat aorta.