Protective effect of flunarizine on blood-brain barrier permeability alterations in acutely hypertensive rats.
OBJECTIVE
Increased cerebrovascular permeability to protein is a well-documented finding in acute and chronic hypertension. In this study, we examined the effect of pretreatment with a calcium entry blocker, flunarizine, on the increased cerebrovascular permeability to protein that develops in norepinephrine-induced acute hypertension.


METHODS
Protein transfer was assessed qualitatively with Evans blue dye and quantitatively with iodine-125-labeled serum albumin.


RESULTS
Brains of hypertensive rats showed increased permeability to both tracers. The number and size of the areas of Evans blue extravasation were smaller in the hypertensive groups pretreated with flunarizine intravenously. This was supported by the quantitative studies, which demonstrated a significant decrease in protein transfer in total brain of hypertensive rats pretreated with intravenous flunarizine, 1 mg/kg (p less than 0.005) and 2.5 mg/kg (p less than 0.001). Data from individual brain regions showed that pretreatment with flunarizine resulted in significant reduction of protein transfer in most brain regions.


CONCLUSIONS
These data support the hypothesis that calcium plays a role in increased cerebral endothelial permeability in hypertension.
Department of Pathology Neuropathology, Queen's University, Kingston, Ontario, Canada.
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D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D005070:Evans Blue / Q000493:pharmacokinetics*; D005444:Flunarizine / Q000008:administration & dosage / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007457:Iodine Radioisotopes; D008297:Male; D009638:Norepinephrine / Q000633:toxicity; D051381:Rats; D011920:Rats, Inbred WF; D012709:Serum Albumin / Q000493:pharmacokinetics*
D007457:Iodine Radioisotopes; D012709:Serum Albumin; D005070:Evans Blue; D005444:Flunarizine; D002118:Calcium; D009638:Norepinephrine