Sympathetic α3β2‐nAChRs mediate cerebral neurogenic nitrergic vasodilation

Abstract

The nicotinic acetylcholine receptor (nAChR) on the sympathetic nerves innervating cerebral arteries of the pig crossbreed between Landrace and Yorkshire (LY) in Illinois is α7‐nAChR. Nicotine‐induced cerebral neurogenic vasodilation in pigs crossbreed among Landrace, Yorkshire and Duroc (LYD) in Hualien (Taiwan), however, is not blocked by α‐bungarotoxin (α‐BTGX, a highly selective α7‐nAChR antagonist). The cerebral perivascular sympathetic nAChR subtype of LYD pigs, therefore, was examined. The nicotine‐induced dilatation of isolated basilar arteries was not affected by α‐conotoxin IMI (an α7‐nAChR antagonist) or α‐conotoxin AuIB (an α3β4‐nAChR antagonist). The vasodilation was inhibited by preferential α3‐containing nAChR antagonists (tropinone and tropane) and α‐conotoxin MII (a selective α3β2‐nAChR antagonist). Using reverse transcription PCR, α3‐, α7‐, β2‐ and β4‐subunits of nAChRs were expressed in fresh superior cervical ganglia. The mRNA levels of α3‐, β2‐ and β4‐subunits were significantly higher than that of α7‐subunit. Furthermore, nicotine‐induced inward currents in α3β2‐nAChR‐expresssing oocytes were blocked by α‐conotoxin MII but not by α‐BTGX or α‐conotoxin AuIB. In conclusion, the predominant nAChR on cerebral perivascular sympathetic nerves mediating cerebral nitrergic neurogenic vasodilation in LYD pigs is α3β2‐subtype (supported by TCU & NSC).