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

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.