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Background: Nicotine is one of main chemicals of tobacco smoke and promotes atherosclerosis and stroke. Tobacco smoke is considered an independent risk factor for intracranial aneurysm formation, growth, and rupture. There are mainly 5 subtypes of nicotine receptors. Roles of alpha7 nicotinic acetylcholine receptor (α7nAChR) in inflammation and vascular remodeling are diverse and context-dependent. Notably, endothelial α7nAChR is considered to mediate nicotine-induced inflammation. Activation of endothelial α7nAChR by nicotine may promote aneurysm rupture by increasing the aneurysm wall inflammation. Using a mouse model of intracranial aneurysm, we examined effects of nicotine in aneurysm rupture. Moreover we investigated potential roles of α7nAChR stimulation by nicotine in the pathophysiology of intracranial aneurysms.Methods: Intracranial aneurysms were induced by a combination of elastase injection into the cerebrospinal fluid and deoxycorticosteron acetate-salt (DOCA-salt) hypertension in male mice. Mice were treated with (1) nicotine (5 mg/kg/day, n=25); (2) saline sc (n=22) for three weeks after aneurysm induction. To investigate the effect of α7nAChR, mice were treated with (1) saline sc + saline ip (n=11); (2) saline sc + α7nAChR antagonist (Methyllycaconitine, MLA 5mg/kg/day) ip (n=13); (3) nicotine (5 mg/kg/day, sc, 28 days) + saline ip (n=18); (4) nicotine sc + MLA ip (n=18).Results: Nicotine alone significantly increased aneurysmal rupture compared with saline treatment (89% vs 46%, p=0.009). While α7nAChR antagonist did not affect the incidence of aneurysm or rupture rates, the α7nAChR antagonist significantly reduced the deleterious effect of nicotine as indicated by the reduction of the rupture rates (41% vs 100%: nicotine sc + MLA ip group vs nicotine sc + saline ip group, p=0.027).Conclusion: Our data indicate the promotion of aneurysm rupture by nicotine may be mediated by its stimulation of alpha7nAChR.