Quantitative estimate of pinocytosis in experimental acute hypertension

Abstract

Cerebral cortical arterioles in focal neocortical areas develop increased permeability to plasma proteins and protein tracers in experimental hypertensive encephalopathy. The mechanism underlying this increased permeability has been the subject of several studies. In our previous studies of angiotensin-induced acute hypertension, pinocytosis appeared to be the principal mechanism for the increased blood-brain barrier (BBB) permeability observed. In the present study pinocytotic activity was assessed quantitatively to determine whether enhanced pinocytosis was confined to the permeable arteriolar segments of hypertensive animals. In addition, the effect of horseradish peroxidase (HRP) itself on the pinocytotic activity of normal cerebral cortical arteriolar endothelium was determined. In 12 rats following administration of HRP, hypertension was induced by an infusion of angiotensin. The animals were perfusion-fixed 90 s after the onset of the infusion. Control animals received saline only or HRP only. The area of arteriolar endothelium in cross section was determined by a planimeter from overlapping electron micrographs taken at a constant magnification around the circumference of the vessel wall. Results indicate a significant (P less than 0.001) increase in the number of pinocytotic vesicles in the permeable arteriolar segments of hypertensive animals as compared with nonpermeable arteriolar segments of the same animals and comparable segments of normotensive rats. In addition, eight times as many vesicles appear to be transporting tracer in the permeable arteriolar segments of hypertensive animals as compared to the nonpermeable segments of the same animals and normotensive animals. HRP alone did not affect the pinocytotic index, there being no difference (P greater than 0.05) in the number of vesicles in normotensive animals receiving saline only and those receiving HRP only. Our previous observation that disruption of endothelial cells or their tight junctions did not occur was confirmed.