Alpha7-nicotinic acetylcholine receptors on cerebral perivascular sympathetic nerves mediate choline-induced nitrergic neurogenic vasodilation.
It has been suggested in isolated porcine cerebral arteries that stimulation by nicotine of alpha7-nicotinic acetylcholine receptors (alpha7-nAChRs) on sympathetic nerves, but not direct stimulation of parasympathetic nitrergic nerves, caused nitrergic neurogenic dilation. Direct evidence supporting this hypothesis has not been presented. The present study, which used in vitro tissue bath and confocal microscopy techniques, was designed to determine whether choline, a selective agonist for alpha7-nAChRs, induced sympathetic-dependent nitrergic dilation of porcine basilar arterial rings. Choline and several nAChR agonists induced exclusive relaxation of basilar arterial rings without endothelium. The relaxation was blocked by tetrodotoxin, nitro-L-arginine, guanethidine, and beta2-adrenoceptor antagonists. Furthermore, the relaxation was blocked by methyllycaconitine and alpha-bungarotoxin (preferential alpha7-nAChR antagonists) and mecamylamine but was not affected by dihydro-beta-erythroidine (a preferential alpha4-nAChR antagonist). Confocal microscopic study demonstrated that choline and nicotine induced significant calcium influx in cultured porcine superior cervical ganglionic cells but failed to affect calcium influx in cultured sphenopalatine ganglionic cells, providing direct evidence that choline and nicotine did not act directly on the parasympathetic nitrergic neurons. The increased calcium influx in superior cervical ganglionic cells was attenuated by alpha-bungarotoxin and methyllycaconitine but not by dihydro-beta-erythroidine. These results support our hypothesis that activation of alpha7-nAChRs on cerebral perivascular sympathetic nerves causes calcium influx and the release of norepinephrine, which then act on presynaptic beta2-adrenoceptors located on the neighboring nitrergic nerve terminals, resulting in NO release and vasodilation. Endogenous choline may play an important role in regulating cerebral sympathetic activity and vascular tone.
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Ill 62794-9629, USA.
Min-Liang
ML
Si
Tony J F
TJ
Lee
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D002794:Choline / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D005726:Ganglia, Parasympathetic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D013564:Sympathetic Nervous System / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D019335:Nitroarginine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D011189:Potassium Chloride; D009538:Nicotine; D002794:Choline; D002118:Calcium; D000157:Aconitine