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 (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.