Introduction: Tobacco smoking is an independent risk factor for intracranial aneurysmal rupture. Nicotine is one of main chemicals of tobacco smoke that promotes atherosclerosis and stroke. Nicotine induces vascular remodeling through activation of α7nicotinic acetylcholine receptor (α7nAChR) that is expressed in the vascular wall. Using a mouse model of intracranial aneurysm, we examined whether the activation of α7nAChR by nicotine promotes intracranial aneurysmal rupture.
Methods and Materials: To induce aneurysm, we combined induced systemic hypertension (deoxycorticosterone acetate-salt hypertension) and a single injection of elastase (17.5mU) into the cerebrospinal fluid at the right basal cistern. We used α7nAChR knockout (α7KO) mice and the wild-type (WT) mice. Mice were treated with (1) nicotine (5 mg/kg/day); (2) vehicle (saline) subcutaneously from one week before aneurysm induction, and the treatments were continued until 21 days after aneurysm induction.
Results: Nicotine treatment significantly increased aneurysmal rupture compared to the vehicle treatment in the WT mice (WT + vehicle vs. WT + nicotine: 46% vs. 84%, P < 0.01). Furthermore, the harmful effect of nicotine was abolished in the α7KO mice compared (WT + nicotine vs. α7KO + nicotine: 84% vs. 27%; P < 0.05). There was no difference in the incidence aneurysmal rupture between the α7KO mice treated with nicotine and the α7KO mice treated with the vehicle (α7KO + nicotine vs. α7KO + vehicle: 27% vs. 44%; P = 1.00).
Conclusion: Our data indicate that α7nAChR mediates nicotine’s promotion of intracranial aneurysmal rupture.