Mechanisms of protection of the blood-brain barrier during acute hypertension in chronically hypertensive rats.

Spontaneously hypertensive rats are less susceptible than normotensive rats to disruption of the blood-brain barrier during acute hypertension. The purpose of this study was to examine mechanisms that protect the blood-brain barrier from disruption in chronically hypertensive rats during acute hypertension. Normotensive Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) were studied using intravital fluorescent microscopy and fluorescein-labeled dextran. Disruption of the blood-brain barrier was characterized by the appearance of microvascular leaky sites and quantitated by the clearance of fluorescein-labeled dextran. We measured pressure (servo null) in pial arterioles and venules 40 to 60 micron in diameter. In WKY, acute, phenylephrine-induced hypertension increased pial arteriolar pressure by 47 +/- 7 mm Hg (mean +/- SE) and pial venous pressure by 20 +/- 2 mm Hg. Leaky sites increased from 0 to 28 +/- 2. In SHRSP, acute hypertension increased pial arteriolar pressure 44 +/- 8 mm Hg, but pial venous pressure increased only 6 +/- 1 mm Hg and leaky sites increased from 0 to only 6 +/- 1. All leaky sites were venular. In another group of WKY and SHRSP, we increased pial venous pressure passively with a neck cuff. In WKY, venous pressure increased by 22 +/- 2 mm Hg, and leaky sites increased from 0 to 23 +/- 2. In SHRSP, venous pressure increased by 19 +/- 1 mm Hg, and leaky sites increased from 0 to 24 +/- 2. Thus, when venous pressure is increased to the same level in WKY and SHRSP, disruption of the blood-brain barrier is similar. We conclude that protection of the blood-brain barrier during acute hypertension in SHRSP is related to attenuation of increases in pial venous pressure, not pial arteriolar pressure, and the blood-brain barrier in venules of SHRSP probably is not inherently resistant to disruption.