Nicotine raises the influx of permeable solutes across the rat blood-Brain barrier with little or no capillary recruitment

J. L. Chen, L. Wei, D. Bereczki, F. J. Hans, T. Otsuka, V. Acuff, J. F. Ghersi-Egea, C. Patlak, J. D. Fenstermacher

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Nicotine (1.75 mg/kg s.c.) was administered to rats to raise local CBF (1CBF) in various parts of the brain, test the capillary recruitment hypothesis, and determine the effects of this increase in 1CBF on local solute uptake by brain. 1CBF 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 1CBF 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 1CBF 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.

Original languageEnglish
Pages (from-to)687-698
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume15
Issue number4
DOIs
Publication statusPublished - Jan 1 1995

Keywords

  • 3-O-Methylglucose
  • Antipyrine
  • Brain activation
  • Local cerebral blood flow
  • Permeability-surface area product

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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