Lee RH, Liu YQ, Chen PY, Liu CH, Chen MF, Lin HW, Kuo JS, Premkumar LS, Lee TJ. Sympathetic ␣32-nAChRs mediate cerebral neurogenic nitrergic vasodilation in the swine. Am J Physiol Heart Circ Physiol 301: H344 -H354, 2011. First published May 2, 2011; doi:10.1152/ajpheart.00172.2011.-The ␣7-nicotinic ACh receptor (␣7-nAChR) on sympathetic neurons innervating basilar arteries of pigs crossed bred between Landrace and Yorkshire (LY) is known to mediate nicotine-induced, -amyloid (A)-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 A and ␣-bungarotoxin (␣-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 A, ␣-BGTX, and ␣-conotoxin IMI (␣7-nAChR antagonists), or ␣-conotoxin AuIB (␣34-nAChR antagonist) but was inhibited by tropinone and tropane (␣3-containing nAChR antagonists) and ␣-conotoxin MII (selective ␣ 32-nAChR antagonist). Nicotine-induced inward currents in ␣ 32-nAChR-expressing oocytes were inhibited by ␣-conotoxin MII but not by ␣-BGTX, A, or ␣-conotoxin AuIB. mRNAs of ␣ 3-, ␣7-, 2-, and 4-subunits were expressed in both SCGs and MCGs with significantly higher mRNAs of ␣ 3-, 2-, and  4-subunits than that of ␣7-subunit. The A-insensitive sympathetic ␣ 32-nAChR mediates nicotine-induced cerebral nitrergic neurogenic vasodilation in LYD pigs. The different finding from A-sensitive ␣ 7-nAChR in basilar arteries of LY pigs may offer a partial explanation for different sensitivities of individuals to A in causing diminished cerebral nitrergic vasodilation in diseases involving A.␣ 32-nicotinic ACh receptor; axo-axonal interaction; -amyloid; cerebral perivascular sympathetic nerves; superior cervical ganglion IT IS WELL ESTABLISHED THAT cerebral arteries receive dense sympathetic innervation originating in the superior cervical ganglion (SCG) (24, 50) and that nicotinic ACh receptors (nAChRs) on the nerve terminals regulate norepinephrine (NE) release (50). In the pigs crossbred between Landrace and Yorkshire in the United States, activation by nicotinic agonists of the nAChRs on perivascular sympathetic nerves innervating cerebral arteries results in release of NE, which then causes release of nitric oxide (NO) from the nearby parasympathetic nitrergic nerves and dilation of the arteries (22, 39). This nicotinic agonist-induced axo-axonal interaction leading to nitrergic vasodilation is mediated by the ␣ 7 -nAChR subtype (39). The vasodilation is blocked by -amyloid peptide (A) via inhib...