MECHANISMS UNDERLYING CEREBROVASCULAR EFFECTS OF CIGARETTE-SMOKING INRATS IN-VIVO

Background and Purpose-The effects of acute smoking on cerebral circul ation are controversial. This study was designed (1) to clarify any di fferences between the effects of cigarette smoking and nicotine infusi on and between the effects of single- and multiple-cigarette smoking o n cerebral vessels and (2) to probe the mechanism(s) underlying the va scular responses. Methods-In pentobarbital-anesthetized, mechanically ventilated Sprague-Dawley rats, pial vessel diameters were measured wi th the use of a cranial window preparation. We studied the effects of (1) 60 puffs per minute of mainstream cigarette smoke from cigarettes having 2 nicotine levels (0.1 and 1 mg per cigarette), (2) administrat ion of nicotine (0.05 mg per body IV), and (3) repeated smoking (four I mg nicotine-containing cigarettes at 30-minute intervals) (n=6 each) . Results-Inhalation of smoke from a 0.1 or 1 mg nicotine-containing c igarette for I minute caused pial arterioles to constrict at 30 second s (7.2% and 7.3%, respectively) and then to dilate (peak at 5 to 10 mi nutes; 4.6% and 17.9%, respectively). Nicotine infusion caused pial va sodilation (35.7%) without an initial vasoconstriction. Repeated smoki ng suppressed the pial vasodilation but not the initial vasoconstricti on. The vasodilation induced by a single cigarette was greatly inhibit ed by pretreatment with mecamylamine or glibenclamide and attenuated b y propranolol or N-omega-nitro-L-arginine methyl ester; the initial va soconstriction was inhibited by seratrodast, a thromboxane A(2) recept or antagonist (n=6 in each case). Conclusions-Single-cigarette smoking had a significant biphasic effect on cerebral arteriolar tone. The va sodilation was attenuated by repeated smoking. The vasodilation is mos t likely an effect of nicotine, at least in part mediated via sympathe tic activation, NO production, and K+ channel activation. The vasocons triction is partially due to thromboxane A(2) induced by cigarette smo ke.