Blood-brain barrier permeability and vascular reactivity to bradykinin after pretreatment with dexamethasone.
The role of kinins as mediator substances is increasingly recognized in cerebral ischemia and trauma. It has previously been shown that cerebral exposure to bradykinin, which causes brain edema, is associated with arteriolar dilatation and selective opening of the blood-brain barrier (BBB) to small molecular weight indicators, such as Na+-fluorescein. Since the evidence suggests that these effects results from an activation of the arachidonic acid cascade, particularly from formation of E- and I-type prostaglandins, therapeutical inhibition of the cerebral effect of bradykinin has been attempted by pretreatment of experimental animals with dexamethasone. The BBB function and changes of the pial vessel diameters were studied by fluorescence microscopy in cats in alpha-chloralose anesthesia during superfusion of the exposed cerebral cortex. After a control phase bradykinin was added to a cerebral superfusate in concentrations of 4 x 10(-8) M to 4 x 10(-3) M. Two additional groups of animals received dexamethasone in a dose of 1, or 5 mg/kg body wt., respectively, 5 h prior to the cerebral superfusion with bradykinin. Na+-fluorescein (mol wt.: 376) was infused intravenously as a BBB indicator. The BBB marker remained strictly confined to the intravascular compartment under control conditions. Pretreatment with dexamethasone did not prevent opening of the BBB by bradykinin, either at the low, or high dose. However, the low dose of dexamethasone blunted the vasodilatory response to bradykinin, whereas the high dose (5 mg/kg) was found to enhance the dilatory properties of bradykinin at concentrations of 4 x 10(-3) M.(ABSTRACT TRUNCATED AT 250 WORDS)
Schürer
L
L
Institut für Chirurgische Forschung, Ludwig-Maximilians-Universität München, Federal Republic of Germany.
Temesvari
P
P
Wahl
M
M
Unterberg
A
A
Baethmann
A
A
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D002415:Cats; D002536:Cerebral Arteries / Q000187:drug effects; D002550:Cerebral Veins / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male
D003907:Dexamethasone; D001920:Bradykinin