Nicotine raises the influx of permeable solutes across the rat blood-brain barrier with little or no capillary recruitment.
Nicotine (1.75 mg/kg s.c.) was administered to rats to raise local CBF (lCBF) in various parts of the brain, test the capillary recruitment hypothesis, and determine the effects of this increase in lCBF on local solute uptake by brain. lCBF as well as the local influx rate constants (K1) and permeability-surface area (PS) products of [14C]antipyrine and [14C]-3-O-methyl-D-glucose (3OMG) were estimated by quantitative autoradiography in 44 brain areas. For this testing, the finding of significantly increased PS products supports the capillary recruitment hypothesis. In 17 of 44 areas, nicotine treatment increased lCBF by 30-150%, K1 of antipyrine by 7-40%, K1 of 3OMG by 5-27%, PS product of antipyrine by 0.20% (mean 7%), and PS product of 3OMG by 0-23% (mean 8%). Nicotine had no effect on blood flow or influx in the remaining 27 areas. The increases in lCBF and K1 of antipyrine were significant, whereas those in K1 of 3OMG and in PS for both antipyrine and 3OMG were not statistically significant. The lack of significant changes in PS products implies that in brain areas where nicotine increased blood flow: (a) essentially no additional capillaries were recruited and (b) blood flow within brain capillary beds rises by elevating linear velocity. The K1 results indicate that the flow increase generated by nicotine will greatly raise the influx and washout rates of highly permeable materials, modestly elevate those of moderately permeable substances, and negligibly change those of solutes with extraction fractions of < 0.2, thereby preserving the barrier function of the blood-brain barrier.
Chen
J L
JL
Department of Neurological Surgery, State University of New York, Stony Brook, USA.
Wei
L
L
Bereczki
D
D
Hans
F J
FJ
Otsuka
T
T
Acuff
V
V
Ghersi-Egea
J F
JF
Patlak
C
C
Fenstermacher
J D
JD
D019325:3-O-Methylglucose; D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D001345:Autoradiography; D001783:Blood Flow Velocity; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002196:Capillaries / Q000502:physiology*; D002199:Capillary Permeability / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004906:Erythrocyte Count; D007700:Kinetics; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012711:Serum Albumin, Radio-Iodinated
D008757:Methylglucosides; D012711:Serum Albumin, Radio-Iodinated; D019325:3-O-Methylglucose; D009538:Nicotine; D000983:Antipyrine