Protective effect of flunarizine on blood-brain barrier permeability alterations in acutely hypertensive rats.

Abstract

Background and Purpose: Increased cerebrovascular permeability to protein is a welldocumented 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 ing/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. (Stroke 1991^2:1265-1269)

A Dual-Tracer Method for Differentiating Transendothelial Transport from Paracellular Leakage in Vivo and in Vitro

“…However, as the two-tracer isotope method uses the same molecule with two different tracers, the method may not differentiate between the involvement of transcellular or paracellular transport pathways in total microvascular permeability. In another study, alterations in blood brain barrier permeability were studied using Evans blue and 125 I-taged albumin (Nag, 1991). However, the probes were infused at separate times and no time-dependent observation of the vascular leakage was performed (Nag, 1991).…”

Effects of Exogenous Excitatory Amino Acid Neurotransmitters on Blood–Brain Barrier Disruption in Focal Cerebral Ischemia

“…Inhibition of NO synthase also decreased BBB permeability in focal ischemia without affecting the non-ischemic cortex [18]. Intraendothelial calcium influx has also been suggested as a mechanism to increase endothelial permeability caused by NMDA [19]. An enhanced pinocytosis rather than a breakdown of interendothelial tight junctions was observed during the intrathecal infusion of NMDA, suggesting cerebral endothelial cell activation as a mechanism [20].…”

Structure and Pathology of the Blood–Brain Barrier

“…Subsequent studies demonstrate that reduced activity of the endothelial ATPases precedes BBB breakdown in chronic hypertension (Nag, 1993). Pretreatment of acutely hypertensive rats with the calcium entry blocker, Flunarizine, decreases the number and size of areas of Evans blue extravasation and results in a significant decrease in protein transfer of I 125 -labeled human serum albumin in total brain as well as in individual brain areas in acute hypertension (Nag, 1991).…”