title: Lack of effect of topically applied nicotine on pial arteriole diameter and blood-brain barrier integrity in the cat.
abstract: 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.
authors.affiliation: Department of Physiology, Ludwig-Maximilians-Universität Munich.
authors.forename: L
authors.initials: L
authors.lastname: Schilling
authors.forename: A
authors.initials: A
authors.lastname: Bultmann
authors.forename: M
authors.initials: M
authors.lastname: Wahl
mesh_terms: 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*
chemical_list: D009538:Nicotine; D000241:Adenosine; D009638:Norepinephrine