Sympathetic α3β2-nAChRs mediate cerebral neurogenic nitrergic vasodilation in the swine

Reggie Hui Chao Lee, Yi Qing Liu, Po Yi Chen, Chin Hung Liu, Mei Fang Chen, Hung Wen Lin, Jon Son Kuo, Louis S. Premkumar, Tony Jer Fu Lee

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The α7-nicotinic ACh receptor (α7-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 (α7-nAChR antagonists), or α-conotoxin AuIB (α3β4-nAChR antagonist) but was inhibited by tropinone and tropane (α3-containing nAChR antagonists) and α-conotoxin MII (selective α3β2-nAChR antagonist). Nicotine-induced inward currents in α3β2-nAChR-expressing oocytes were inhibited by α-conotoxin MII but not by α-BGTX, Aβ, or α-conotoxin AuIB. mRNAs of α3-, α7-, β2-, and β4-subunits were expressed in both SCGs and MCGs with significantly higher mRNAs of α3-, β2-, and β4-subunits than that of α7-subunit. The Aβ-insensitive sympathetic α3β2-nAChR mediates nicotine-induced cerebral nitrergic neurogenic vasodilation in LYD pigs. The different finding from Aβ- sensitive α7-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.

Original languageEnglish (US)
Pages (from-to)H344-H354
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume301
Issue number2
DOIs
StatePublished - Aug 1 2011

Keywords

  • Axo-axonal interaction
  • Cerebral perivascular sympathetic nerves
  • Superior cervical ganglion
  • αβ-nicotinic ach receptor
  • β-amyloid

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Lee, R. H. C., Liu, Y. Q., Chen, P. Y., Liu, C. H., Chen, M. F., Lin, H. W., Kuo, J. S., Premkumar, L. S., & Lee, T. J. F. (2011). Sympathetic α3β2-nAChRs mediate cerebral neurogenic nitrergic vasodilation in the swine. American Journal of Physiology - Heart and Circulatory Physiology, 301(2), H344-H354. https://doi.org/10.1152/ajpheart.00172.2011