Dynamics of experimental vasogenic brain oedema in the rat: changes induced by adrenergic drugs.
The effects of adrenergic drugs on the formation and resolution of cerebral oedema in a rat model of cold-induced vasogenic brain oedema were studied. Evans blue dye extravasation, water content and ultrastructural alterations (pinocytotic vesicle formation in capillary endothelial cells and apparent water accumulation in the brain parenchyma) were evaluated in parietal cortex. Previous administration of the alpha-adrenoceptor antagonist phenoxybenzamine produced a reduction of Evans blue extravasation and water content, diminished vesicle formation and reduced water accumulation. Previous administration of the beta2-adrenoceptor agonist clenbuterol reduced Evans blue extravasation and water content, but did not change vesicle frequency. The effects of clenbuterol on Evans blue passage to the brain were blocked by timolol (beta-adrenoceptor antagonist) but not by metoprolol (selective beta1-adrenoceptor antagonist). When given after the application of cold, clenbuterol was also able to reduce Evans blue and water content in the brain. Isoprenaline (beta-adrenoceptor agonist that does not cross the blood-brain barrier) showed a reduction in Evans blue extravasation only when given intracerebroventricularly. Vinblastine (a drug that prevents vesicle formation) produced a reduction of the amount of pinocytotic vesicles. We conclude that there is an influence of the central adrenergic nervous system on the formation and/or resolution of vasogenic brain oedema and that the alterations on water movement and Evans blue transport mediated by adrenergic drugs seem to be due, at least in part, to alterations of pinocytotic activity in capillary endothelial cells.
Borges
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N
Institute of Pharmacology and Therapeutics, Medical Faculty, Porto, Portugal.
Sarmento
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A
Azevedo
I
I
D018663:Adrenergic Agents / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001929:Brain Edema / Q000473:pathology / Q000503:physiopathology*; D002196:Capillaries / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects*; D002976:Clenbuterol / Q000494:pharmacology; D003080:Cold Temperature; D005070:Evans Blue; D007276:Injections, Intraventricular; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013999:Timolol / Q000494:pharmacology
D018663:Adrenergic Agents; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D010643:Phenoxybenzamine; D005070:Evans Blue; D013999:Timolol; D007545:Isoproterenol; D002976:Clenbuterol