Substance P-induced enhanced permeability of dura mater microvessels is accompanied by pronounced ultrastructural changes, but is not dependent on the density of endothelial cell anionic sites

Abstract

Experimental data point to a determinant role for endothelial cell (EC) anionic sites in the regulation of vascular permeability. Previous studies have shown that EC anionic sites density is reduced in conditions of enhanced permeability. The pathophysiology of migraine and vascular headache encompasses dilatation of dural vessels and extravasation of plasma proteins. The current study was carried out to determine if the density of EC anionic sites is reduced in enhanced permeability of dural vessels. Enhanced permeability was chemically induced in rats by intravenous injection of substance P and was tested by assessing leakage of horseradish peroxidase (HRP). Anionic sites were labelled with cationic colloidal gold and their density was quantified from electron microscopy negatives. Experimental animals showed increased leakage of HRP from dural vessels. However, anionic sites in EC membranes (luminal and abluminal) showed no statistical differences when their mean densities in experimental and control animals were compared. The results indicate that in this model, factors other than the density of anionic sites may be important determinants in the permeability of dural vessels. Such factors may include structural alteration of ECs consistent with an increased permeability. In this study pronounced ultrastructural changes in ECs were noted in experimental animals including widening of intercellular junctions and an increase in the number of EC gaps and vesicles.