Mechanisms underlying cerebrovascular effects of cigarette smoking in rats in vivo.
OBJECTIVE
The effects of acute smoking on cerebral circulation are controversial. This study was designed (1) to clarify any differences between the effects of cigarette smoking and nicotine infusion and between the effects of single- and multiple-cigarette smoking on cerebral vessels and (2) to probe the mechanism(s) underlying the vascular responses.


METHODS
In pentobarbital-anesthetized, mechanically ventilated Sprague-Dawley rats, pial vessel diameters were measured with 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) administration of nicotine (0.05 mg per body IV), and (3) repeated smoking (four 1 mg nicotine-containing cigarettes at 30-minute intervals) (n=6 each).


RESULTS
Inhalation of smoke from a 0.1 or 1 mg nicotine-containing cigarette for 1 minute caused pial arterioles to constrict at 30 seconds (7.2% and 7.3%, respectively) and then to dilate (peak at 5 to 10 minutes; 4.6% and 17.9%, respectively). Nicotine infusion caused pial vasodilation (35.7%) without an initial vasoconstriction. Repeated smoking suppressed the pial vasodilation but not the initial vasoconstriction. The vasodilation induced by a single cigarette was greatly inhibited by pretreatment with mecamylamine or glibenclamide and attenuated by propranolol or Nomega-nitro-L-arginine methyl ester; the initial vasoconstriction was inhibited by seratrodast, a thromboxane A2 receptor antagonist (n=6 in each case).


CONCLUSIONS
Single-cigarette smoking had a significant biphasic effect on cerebral arteriolar tone. The vasodilation was attenuated by repeated smoking. The vasodilation is most likely an effect of nicotine, at least in part mediated via sympathetic activation, NO production, and K+ channel activation. The vasoconstriction is partially due to thromboxane A2 induced by cigarette smoke.
Iida
M
M
Department of Anesthesiology and Critical Care Medicine, Gifu University School of Medicine, Japan.
Iida
H
H
Dohi
S
S
Takenaka
M
M
Fujiwara
H
H
D000818:Animals; D016227:Benzoquinones / Q000097:blood / Q000494:pharmacology; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D002263:Carboxyhemoglobin / Q000032:analysis; D002536:Cerebral Arteries / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006538:Heptanoic Acids / Q000097:blood / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009538:Nicotine / Q000097:blood / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000097:blood / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000097:blood / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D016227:Benzoquinones; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D006538:Heptanoic Acids; D007004:Hypoglycemic Agents; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011448:Prostaglandin Antagonists; D014665:Vasodilator Agents; C060230:seratrodast; D008464:Mecamylamine; D009538:Nicotine; D002263:Carboxyhemoglobin; D011433:Propranolol; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester