The Blood-Brain Barrier in Acute and Chronic Hypertension

Abstract

Acute arterial hypertension, induced by vasoactive substances or by compression of the thoracic aorta, can increase the permeability of the blood-brain barrier (BBB) in experimental animals (1). The present review deals predominantly with the BBB to macromolecules, since that is the BBB function most commonly studied in experimental hypertension. The abnormal permeability associated with hypertension has a typical, patchy appearance, although the pattern varies somewhat with different experimental models (see beZow and 1-6). This BBB dysfunction, which is rapidly reversible when the pressure returns to normal levels (7), is a direct consequence of the increased mechanical stress on the endothelial cells caused by the high intravascular pressure (1). An early hypothesis stating that the increased permeability was due to ischemia has been refuted for the following reasons: 1) the increased permeability to macromolecules is evident within seconds after the pressure increase, while it takes much longer for ischemia to cause this change in the BBB (1); 2) the cerebral blood flow is higher in areas with disturbed permeability than in surrounding tissue (8,9); and 3) energy metabolism in the brain is not disturbed in shortlasting acute hypertension (10,11). Moreover, a local increase of the intraluminal pressure in a carotid artery, induced by infusion of blood or isotonic saline, results in a similar BBB dysfunction to that caused by acute systemic hypertension (12-15).The ischemia hypothesis was based on the "vasospasm" theory. Cerebral arteries and arterioles constrict during acute hypertension,

Adrenergic-Induced Enhancement of Brain Barrier System Permeability to Small Nonelectrolytes: Choroid Plexus versus Cerebral Capillaries

“…Propranolol (3 mg/kg) in rats not in jected with pressor agents did not alter the penetra tion of tracer urea or mannitol into various CNS regions. Similarly, propranolol does not alter RIBSA penetration into rat brain (Sankar et al, 1981 (Johansson, 1980). This investiga tion indicates that the blood-CSF barrier, as well as the BBB, is disrupted consequent to sudden eleva tion in MABP.…”

“…The degree of BBB dysfunction has been in timately linked to the rate of rise, and peak, of blood pressure (Domer et aI., 1980;Johansson, 1980). Increased penetration of tracers from blood to brain occurs whether blood pressure is elevated by pressor agents or by intravascular infusion of saline or blood (Rapoport, 1976;Hardebo, 1980).…”

“…In addition, dibutyryl cyclic AMP (10 mg/kg i. v. ), a stimulator of pinocytosis in the BBB, did not alter the 30-min Vd of [ 3 H]mannitol or [ 1 4C]dextran in any region analyzed in normotensive rats (V A. Murphy and C. E. Johanson, unpublished observation). How ever, it is not possible to rule out a pinocytotic com ponent of tracer movement into brain (and CSF) in acute hypertension, since SITS blocks RIBSA movement into eNS (Johansson, 1980). Indeed, there is substantial evidence that both mechanisms (Fig.…”

“…Adrenergic agonists that raise blood pressure can open the blood-brain barrier (BBB) to large mole cules such as albumin and horseradish peroxidase and to smaller molecules like inulin and norepi nephrine (Johansson, 1980). Metaraminol, epineph rine, amphetamine, norepinephrine, and phenyl ephrine increase BBB permeability, but if the agent induced rise in blood pressure is blocked, no change in tracer permeation is observed (Johansson, 1980).…”

“…Metaraminol, epineph rine, amphetamine, norepinephrine, and phenyl ephrine increase BBB permeability, but if the agent induced rise in blood pressure is blocked, no change in tracer permeation is observed (Johansson, 1980). A rise in intracarotid pressure concurrent with sys temic hypervolemia also opens the BBB (Nagy et aI., 1979).…”