Lack of effect of topically applied nicotine on pial arteriole diameter and blood-brain barrier integrity in the cat.
In the present study, the vasomotor effects of nicotine, its interaction with local chemical factors and norepinephrine, and its effects on the permeability of the blood-brain barrier (BBB) were investigated. Using perivascular microapplication, 10(-6) M nicotine was found not to exert a vasomotor effect by itself or to modify the vasodilating effect of an increase in perivascular H+, K+ and adenosine concentration. The constrictor effect of a decrease in H+, K+ or an increase in norepinephrine concentration in the perivascular space was also not altered by 10(-6) M nicotine, indicating a lack of interaction between nicotine and the compounds tested. Using cortical superfusion and intravital fluorescence microscopy nicotine (10(-7) to 10(-3) M) was also found not to affect the diameter of pial arteries during superfusion periods of 30 min each. The integrity of BBB could be demonstrated in time-matched solvent controls over 3 h using intravenously-infused FITC-labelled dextran (MW 70,000) as tracer. During cortical superfusion with 10(-7) to 10(-5) M nicotine the permeability of the BBB was not increased compared with the time-matched controls. However, during superfusion with 10(-4) and 10(-3) M nicotine, tracer extravasation could be quantified by computer-aided image analysis. The extravasation index (EI) increased by up to eight times. These data indicate that only toxic concentrations of nicotine increase BBB permeability to FITC-dextran 70,000.
Schilling
L
L
Department of Physiology, Ludwig-Maximilians-Universität Munich.
Bultmann
A
A
Wahl
M
M
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002415:Cats; D004347:Drug Interactions; D005260:Female; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects*
D009538:Nicotine; D000241:Adenosine; D009638:Norepinephrine