Pathophysiology of the opening of the blood-brain and blood-cerebrospinal fluid barriers in acute hypertension.

Acute hypertension, produced by i.v. Aramine injection, opened the blood-brain and blood-cerebrospinal fluid (CSF) barriers to Evans blue-albumin. In rabbits the threshold for blood-brain barrier (B-BB) opening was approximately 160 mm Hg and for blood--CSF barrier opening 150 mm Hg. The blood-brain and blood-CSF barriers were not opened by blood pressure elevations less than 80 mm Hg. Multiple blue spots (1- to 10-mm diameter) which show Evans blue-albumin extravasation, were seen throughout the cerebral cortex, occasionally in the medulla-pons, and cerebellum. Diffuse extravasation was not seen and the extravasation was nearly symmetrical in the two hemispheres. The barrier permeability was increased when systemic blood pressure was elevated rapidly rather than gradually to the threshold level. Endothelial or epithelial cell destruction was never observed in light and electron microscopic studies. Arterial blood and CSF PCO2, PO2 and pH remained constant, which is indicative of the lack of significant metabolic effect caused by hypertension. Barrier opening in acute hypertension is postulated to be due primarily to the direct mechanical effect of increased intraluminal pressure in cerebral vessels, which may cause widening of the tight junctions between endothelial cells.