Blood-brain barrier opening to horseradish peroxidase in acute arterial hypertension

Summary Acute arterial hypertension was induced in male Wistar rats using two experimental techniques: (1) i.v. injection of Aramine and (2) infusion of physiological saline as a bolus via internal carotid artery. Horseradish peroxidase (HRP) was injected i.v. prior to both experimental procedures and subsequently localized in the brain by light and electron microscopy. In the saline infusion (pressure pulse) model, colloidal lanthanum was also applied as a diffusion tracer following fixation of the cerebral endothelium.In the Aramine model, extravasation of HRP correlated with abrupt elevation of blood pressure. In the pressure pulse model HRP extravasation was consistently visualized in the affected hemisphere. Electron microscopy showed consistent labeling of plasmalemmal vesicles by HRP in segments of cerebral endothelium. However, HRP was also clearly visualized in junctional pools suggesting focal opening of endothelial tight junctions as a pathway for extravasation of this tracer in both hypertensive models. Colloidal lanthanum not transported by plasmalemmal vesicles across endothelium after fixation of the brain also bypassed consecutive membrane appositions of endothelial tight junctions indicating existance of interendothelial pathways to macromolecules in acute arterial hypertension.Supported in part by Medical Research Council of Canada Grant MA-5958Dr. Z. Nagy, Assistant Professor at the Psychiatric Clinic, Semmelweis Medical School, Budapest, Hungary, held a Medical Research Council of Canada Fellowship at the Montreal Neurological Institute, McGill University, during the course of this study