title: Sympathetic α₃β₂-nAChRs mediate cerebral neurogenic nitrergic vasodilation in the swine.
abstract: The α(7)-nicotinic ACh receptor (α(7)-nAChR) on sympathetic neurons innervating basilar arteries of pigs crossed bred between Landrace and Yorkshire (LY) is known to mediate nicotine-induced, β-amyloid (Aβ)-sensitive nitrergic neurogenic vasodilation. Preliminary studies, however, demonstrated that nicotine-induced cerebral vasodilation in pigs crossbred among Landrace, Yorkshire, and Duroc (LYD) was insensitive to Aβ and α-bungarotoxin (α-BGTX). We investigated nAChR subtype on sympathetic neurons innervating LYD basilar arteries. Nicotine-induced relaxation of porcine isolated basilar arteries was examined by tissue bath myography, inward currents on nAChR-expressing oocytes by two-electrode voltage recording, and mRNA and protein expression in the superior cervical ganglion (SCG) and middle cervical ganglion (MCG) by reverse transcription PCR and Western blotting. Nicotine-induced basilar arterial relaxation was not affected by Aβ, α-BGTX, and α-conotoxin IMI (α(7)-nAChR antagonists), or α-conotoxin AuIB (α(3)β(4)-nAChR antagonist) but was inhibited by tropinone and tropane (α(3)-containing nAChR antagonists) and α-conotoxin MII (selective α(3)β(2)-nAChR antagonist). Nicotine-induced inward currents in α(3)β(2)-nAChR-expressing oocytes were inhibited by α-conotoxin MII but not by α-BGTX, Aβ, or α-conotoxin AuIB. mRNAs of α(3)-, α(7)-, β(2)-, and β(4)-subunits were expressed in both SCGs and MCGs with significantly higher mRNAs of α(3)-, β(2)-, and β(4)-subunits than that of α(7)-subunit. The Aβ-insensitive sympathetic α(3)β(2)-nAChR mediates nicotine-induced cerebral nitrergic neurogenic vasodilation in LYD pigs. The different finding from Aβ-sensitive α(7)-nAChR in basilar arteries of LY pigs may offer a partial explanation for different sensitivities of individuals to Aβ in causing diminished cerebral nitrergic vasodilation in diseases involving Aβ.
authors.affiliation: Institutes of Medical Sciences, College of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Reggie Hui-Chao
authors.initials: RH
authors.lastname: Lee
authors.forename: Yi-Qing
authors.initials: YQ
authors.lastname: Liu
authors.forename: Po-Yi
authors.initials: PY
authors.lastname: Chen
authors.forename: Chin-Hung
authors.initials: CH
authors.lastname: Liu
authors.forename: Mei-Fang
authors.initials: MF
authors.lastname: Chen
authors.forename: Hung-Wen
authors.initials: HW
authors.lastname: Lin
authors.forename: Jon-Son
authors.initials: JS
authors.lastname: Kuo
authors.forename: Louis S
authors.initials: LS
authors.lastname: Premkumar
authors.forename: Tony Jer-Fu
authors.initials: TJ
authors.lastname: Lee
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000294:innervation*; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D008297:Male; D008564:Membrane Potentials; D009213:Myography; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D026602:Nitrergic Neurons / Q000187:drug effects / Q000378:metabolism*; D009865:Oocytes; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000378:metabolism*; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014981:Xenopus
chemical_list: D016229:Amyloid beta-Peptides; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C419362:nicotinic receptor alpha3beta2