Fentanyl Attenuates α1B-Adrenoceptor-Mediated Pulmonary Artery Contraction

Background: The authors tested the hypothesis that the intravenous anesthetic fentanyl would attenuate the pulmonary vasoconstrictor response to [alpha]1-adrenoceptor activation. They also investigated the [alpha]1-adrenoceptor subtypes that could potentially mediate this effect of fentanyl.

Methods: Endothelium-denuded canine pulmonary arterial rings were suspended for isometric tension recording. Dose-response curves for the [alpha]1-adrenoceptor agonist phenylephrine were generated in the absence and presence of fentanyl. The effects of inhibiting [alpha]2 (rauwolscine), [alpha]1 (prazosin), [alpha]1A (5-methylurapidil), [alpha]1B (chloroethylclonidine), and [alpha]1D (BMY 7378) adrenoceptors on phenylephrine contraction were also investigated. Receptor "protection" studies were performed to investigate the specific role of [alpha]1B adrenoceptors in mediating fentanyl-induced changes in phenylephrine contraction. Finally, competition binding studies were performed in rat-1 fibroblasts stably transfected with human [alpha]1-adrenoceptor complementary DNAs corresponding to the [alpha]1A-, [alpha]1B-, or [alpha]1D-adrenoceptor subtypes to directly assess whether fentanyl can compete for the [alpha]1-adrenoceptor activation pocket.

Results: Fentanyl attenuated phenylephrine contraction in a dose-dependent fashion. Rauwolscine had no effect on phenylephrine contraction. Phenylephrine contraction was inhibited by prazosin and abolished by chloroethylclonidine but was relatively resistant to inhibition by 5-methylurapidil and BMY 7378. Pretreatment with fentanyl before exposure to chloroethylclonidine increased the maximal contractile response to phenylephrine compared to chloroethylclonidine pretreatment alone. Competition binding studies revealed that fentanyl binds to all three [alpha]1-adrenoceptor subtypes, with a fivefold greater affinity for the [alpha]1B-adrenoceptor compared with the [alpha]1D-adrenoceptor subtype.