The pathogenesis of cerebrovascular lesions in hypertensive rats.
In this study we investigated the pathogenesis of hypertensive cerebrovascular lesions by light microscopy, immunohistochemistry, scanning electron microscopy, and transmission electron microscopy. The brains of rats with experimentally induced hypertension exhibited severe edema and intracerebral hemorrhage. Light microscopy of the arteries showed severe medial lesions and the deposition of fibrinoid substance in the intima. Immunohistochemistry showed that intercellular adhesion molecule (ICAM)-1, platelet-endothelial cell adhesion molecule (PECAM)-1, interleukin (IL)-1alpha, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha endothelial cell expression was upregulated. Scanning electron microscopy of these arteries revealed the adhesion of neutrophils, monocytes, and a few platelets to endothelial cells, and their invasion of endothelial cell junctions and opened junctions. Transmission electron microscopy showed neutrophil and monocyte adhesion to the endothelial cells and neutrophil and monocyte invasion of endothelial cell junctions, intimal deposition of fibrinoid substance, and severe medial cell injury. Intravenously injected horseradish peroxidase insulated from endothelial cell junctions and, via pinocytotic vesicles, into the subendothelial space. These findings suggest that hypertension activates endothelial cells to increase the expression of adhesion molecules and cytokines, and induces neutrophil and monocyte adhesion and migration, resulting in endothelial cell injury and increased permeability of endothelial cells, which results in hypertensive arterial disease.
Suzuki
K
K
Division of Histopathology, Department of Laboratory Sciences, Gunma University School of Health Sciences, 3-39-15 Showamachi, Maebashi, Gunma 371-8514, Japan. ksuzuki@health.gunma-u.ac.jp
Masawa
N
N
Takatama
M
M
D000818:Animals; D002448:Cell Adhesion; D002536:Cerebral Arteries / Q000473:pathology* / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000473:pathology* / Q000648:ultrastructure; D006973:Hypertension / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008297:Male; D008855:Microscopy, Electron, Scanning; D009504:Neutrophils / Q000502:physiology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1