Jl. Chen et al., NICOTINE RAISES THE INFLUX OF PERMEABLE SOLUTES ACROSS THE RAT BLOOD-BRAIN-BARRIER WITH LITTLE OR NO CAPILLARY RECRUITMENT, Journal of cerebral blood flow and metabolism, 15(4), 1995, pp. 687-698
Nicotine (1.75 mg/kg s.c.) was administered to rats to raise local CBF
(ICBF) in various parts of the brain, test the capillary recruitment
hypothesis, and determine the effects of this increase in ICBF on loca
l solute uptake by brain. ICBF as well as the local influx rate consta
nts (K-1) and permeability-surface area (PS) products of [C-14]antipyr
ine and [C-14]-3-O-methyl-D-glucose (30MG) were estimated by quantitat
ive autoradiography in 44 brain areas. For this testing, the finding o
f significantly increased PS products supports the capillary recruitme
nt hypothesis. In 17 of 44 areas, nicotine treatment increased ICBF by
30-150%, K, of antipyrine by 7-40%, K-1 of 30MG by 5-27%, PS product
of antipyrine by 0-20% (mean 7%), and PS product of 30MG by 0-23% (mea
n 8%). Nicotine had no effect on blood flow or influx in the remaining
27 areas. The increases in ICBF and K, of antipyrine were significant
, whereas those in K, of 30MG and in PS for both antipyrine and 30MG w
ere 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 vel
ocity. The K-1 results indicate that the flow increase generated by ni
cotine will greatly raise the influx and washout rates of highly perme
able materials, modestly elevate those of moderately permeable substan
ces, and negligibly change those of solutes with extraction fractions
of <0.2, thereby preserving the barrier function of the blood-brain ba
rrier.