Adrenergic influences on the control of blood-brain barrier permeability.
The central adrenergic innervation of the cerebral microvessels may play a role in the control of blood-brain barrier permeability. To pursue the study of this hypothesis we investigated the effect of noradrenaline on both the permeability of the blood-brain barrier to sodium fluorescein and on the pinocytotic activity of cerebral endothelial cells in the rat. Noradrenaline, stereotactically injected in the right lateral cerebral ventricle, significantly increased the cerebral extraction ratio of sodium fluorescein in a dose-dependent way. The same effect was induced by phenylephrine. Prostaglandin F2 alpha had no significant effect on the passage of sodium fluorescein through the blood-brain barrier. The effect of noradrenaline (150 micrograms) on the cerebral extraction ratio of sodium fluorescein was totally blocked by phenoxybenzamine (25 mg/kg i.p., 24 h before noradrenaline). Noradrenaline (150 micrograms) significantly increased the pinocytotic activity of cerebral endothelial cells. Phenoxybenzamine (as above) reduced the effect of noradrenaline on pinocytosis. It is concluded that noradrenaline increases the blood-brain barrier's permeability to sodium fluorescein, most probably through an effect on alpha adrenoceptors. The increase induced in the blood-brain barrier's permeability by noradrenaline seems to be due, at least in part, to an increase in the pinocytotic activity of endothelial cells.
Sarmento
A
A
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Borges
N
N
Azevedo
I
I
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000098:blood supply*; D002196:Capillaries / Q000294:innervation / Q000648:ultrastructure; D002552:Cerebral Ventricles / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000648:ultrastructure; D019793:Fluorescein; D005452:Fluoresceins / Q000032:analysis; D007276:Injections, Intraventricular; D008854:Microscopy, Electron; D009638:Norepinephrine / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D010643:Phenoxybenzamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010873:Pinocytosis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha
D005452:Fluoresceins; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D010656:Phenylephrine; D015237:Dinoprost; D019793:Fluorescein; D009638:Norepinephrine