title: Dexmedetomidine Inhibits Phenylephrine-induced Contractions via Alpha-1 Adrenoceptor Blockade and Nitric Oxide Release in Isolated Rat Aortae.
abstract: The goal of thisin vitrostudy was to examine the effect of the alpha-2 adrenoceptor agonist dexmedetomidine on phenylephrine (alpha-1 adrenoceptor agonist)-induced contraction in isolated rat aortae and to elucidate the associated cellular mechanisms, with a particular focus on alpha-1 adrenoceptor antagonism. Dexmedetomidine dose-response curves were generated in isolated endothelium-intact and endothelium-denuded rat aortae precontracted with phenylephrine or 5-hydroxytryptamine. Endothelium-denuded aortic rings were pretreated with either dexmedetomidine or the reversible alpha-1 adrenoceptor antagonist phentolamine, followed by post-treatment with the irreversible alpha-1 adrenoceptor blocker phenoxybenzamine. Control rings were treated with phenoxybenzamine alone. All rings were repeatedly washed with Krebs solution to remove all pretreatment drugs, including phenoxybenzamine, phentolamine and dexmedetomidine. Phenylephrine dose-response curves were then generated. The effect of rauwolscine on the dexmedetomidine-mediated change in phenylephrine-induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells was examined using western blotting. The magnitude of the dexmedetomidine-mediated inhibition of phenylephrine-induced contraction was higher in endothelium-intact aortae than in endothelium-denuded aortae or endothelium-intact aortae treated with Nω-nitro-L-arginine methyl ester. However, dexmedetomidine did not significantly alter 5-hydroxytryptamine-induced contraction. In further experiments, prazosin attenuated dexmedetomidine-induced contraction. Additionally, pretreatment with either dexmedetomidine plus phenoxybenzamine or phentolamine plus phenoxybenzamine produced greater phenylephrine-induced contraction than phenoxybenzamine alone, suggesting that dexmedetomidine protects aortae from the alpha-1 adrenoceptor blockade induced by phenoxybenzamine. Rauwolscine attenuated the dexmedetomidine-mediated enhancement of phenylephrine-induced eNOS phosphorylation. Taken together, these results suggest that dexmedetomidine attenuates phenylephrine-induced contractions via alpha-1 adrenoceptor blockade and endothelial nitric oxide release in the isolated rat aorta.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Byon
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju, 52727, Republic of Korea.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Ok
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju, 52727, Republic of Korea.
authors.forename: Soo Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju, 52727, Republic of Korea.
authors.forename: Sebin
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju, 52727, Republic of Korea.
authors.forename: Youngil
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Changwon Hospital, Changwon, 51427, Republic of Korea.
authors.forename: Jeong Yeol
authors.initials: JY
authors.lastname: Han
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju, 52727, Republic of Korea;; Institute of Health Sciences, Gyeongsang National University, Jinju-si, Republic of Korea.
authors.forename: Ju-Tae
authors.initials: JT
authors.lastname: Sohn
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism*; D020927:Dexmedetomidine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D010643:Phenoxybenzamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology
chemical_list: D000322:Adrenergic Agonists; D011941:Receptors, Adrenergic; D010643:Phenoxybenzamine; D010656:Phenylephrine; D009569:Nitric Oxide; D012701:Serotonin; D020927:Dexmedetomidine
keywords: alpha-1 adrenoceptor; alpha-2 adrenoceptor agonist; aorta; contraction; dexmedetomidine; nitric oxide.; phenoxybenzamine; phentolamine; phenylephrine