Ultrastructural changes in endothelial cells of cerebral microvessels after exposure to nitric oxide donor

Abstract

It has been largely accepted that nitric oxide (NO) plays an important role in cerebral vasomotor control. NO has also been proposed to be a significant chemical in the process of endothelial cell injuries in various pathological conditions. Although the toxic effect of high concentrations of NO has been shown, only a few ultrastructural studies have been reported. The purpose of this study is to demonstrate physiological and pathological changes in cerebral microvessels after exposure to a high dose of NO donor. Glyceryl trinitrate, a NO donating chemical, was administered intravenously (10 mg/kg) to experimental rats. The vasomotor response was monitored by in vivo fluorescein videomicroscopy and ultrastructural changes were studied using transmission electron microscopy. The result showed long‐lasting vasodilatation of pial microvessels. The greatest response was observed in microvessels with baseline diameter of less than 10 μm compared with microvessels of a larger diameter (P = 0.003). Exposure to NO donor produced considerable changes in the ultrastructure of cerebral microvessels. Such morphological changes were characterized by increased pinocytosis, increased microvillous formation, mitochondrial swelling, doming of the endothelial surface, swelling of the perivascular astrocytic foot plate and partial separation of endothelial cells from the adjacent brain tissue. These results confirm the cytotoxic effect of NO on cerebral endothelial cell and further elaborate the role of this substance in endothelial cell injury observed in various conditions.