Adrenergic-induced enhancement of brain barrier system permeability to small nonelectrolytes: choroid plexus versus cerebral capillaries.
Acute hypertension induced by adrenergic agents opens up the blood-CSF barrier (choroid plexus) to nonelectrolyte and protein tracers. Sprague-Dawley adult rats anesthetized with ketamine were given an intravenous bolus of either epinephrine (10 micrograms/kg), phenylephrine (100 micrograms/kg), isoproterenol (10 micrograms/kg), or D,L-amphetamine (2 mg/kg). Tracers were injected simultaneously with test agents, and the animals killed 10 min later. Epinephrine raised MABP by 57 mm Hg, to a peak pressure of 160 mm Hg; and it increased the volume of distribution (Vd) of urea, mannitol, and 125I-bovine serum albumin in CSF by 1.5-, 2.7-, and 30-fold, respectively. There was enhanced uptake by lateral and fourth ventricle choroid plexuses, cerebral cortex, cerebellum, medulla, and thalamus. Phenylephrine also elevated MABP to 160 mm Hg, but it increased permeation of tracers into CSF (and several brain regions) to a lesser extent than epinephrine, attributable to protective vasoconstriction associated with alpha-agonist activity. Ratio analysis of Vd data provides evidence that augmented permeation of nonelectrolyte tracers in acute hypertension occurs predominantly by diffusion rather than vesicular transport. It is postulated that elevated MABP distends the central cores of choroid plexus villi and cerebral capillaries, with resultant stretching and opening of tight junctions in both barrier systems; with less hindrance to diffusion, urea and mannitol are cleared at rates closer to free diffusion. Neither isoproterenol (decreased MABP by 40 mm Hg) nor amphetamine (did not alter MABP) significantly opened the choroid plexus or blood-brain barrier to tracers.
D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D001769:Blood / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D002250:Carbon Radioisotopes; D002555:Cerebrospinal Fluid / Q000378:metabolism; D002831:Choroid Plexus / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008353:Mannitol / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium; D014508:Urea / Q000378:metabolism
D002250:Carbon Radioisotopes; D014316:Tritium; D010656:Phenylephrine; D008353:Mannitol; D014508:Urea; D007545:Isoproterenol; D000086:Acetazolamide; D004837:Epinephrine