Fentanyl attenuates α1B-adrenoceptor-mediated pulmonary artery contraction

Abstract

Background: The authors tested the hypothesis that the intravenous anesthetic fentanyl would attenuate the pulmonary vasoconstrictor response to α1-adrenoceptor activation. They also investigated the α1-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 α1-adrenoceptor agonist phenylephrine were generated in the absence and presence of fentanyl. The effects of inhibiting α2 (rauwolscine), α1 (prazosin), α1A (5-methylurapidil), α1B (chloroethylclonidine), and α1D (BMY 7378) adrenoceptors on phenylephrine contraction were also investigated. Receptor "protection" studies were performed to investigate the specific role of α1B adrenoceptors in mediating fentanyl-induced changes in phenylephrine contraction. Finally, competition binding studies were performed in rat-1 fibroblasts stably transfected with human α1A-adrenoceptor complementary DNAs corresponding to the α1A-, α1B-, or α1D- adrenoceptor subtypes to directly assess whether fentanyl can compete for the α1-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 α1B- adrenoceptor subtypes, with a fivefold greater affinity for the α1B-adrenoceptor compared with the α1D- adrenoceptor subtype. Conclusion: Phenylephrine-induced contraction is primarily mediated by α1B-adrenoceptor activation in canine pulmonary artery. Fentanyl attenuates phenylephrine contraction by binding to α1B adrenoceptors. © 2005 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.