PROTECTIVE EFFECT OF FLUNARIZINE ON BLOOD-BRAIN-BARRIER PERMEABILITY ALTERATIONS IN ACUTELY HYPERTENSIVE RATS

Background and Purpose: 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 < 0.005) and 2.5 mg/kg (p < 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.