Endothelial cell shrinkage increases permeability through a Ca²⁺‐dependent pathway in single frog mesenteric microvessels

Abstract

The aim of this study was to investigate further the hypothesis that a change in the endothelial cell (EC)-extracellular matrix (ECM) attachment may modify the increase in capillary permeability caused by endothelial cell shrinkage. In intact microvessels of the frog mesentery, we have shown that endothelial cell shrinkage after exposure to a hypertonic solution (330 versus 230 mosmol l¢ in frog Ringer solution) did not increase hydraulic permeability (Lp) when vessels were perfused with a normal Ringer solution containing bovine serum albumin (BSA). However, when vessels were pretreated with a hexapeptide containing the Arg-Gly-Asp (RGD) sequence, which competes for the binding sites between endothelial cell integrins and the basement membrane, and reduces the number of functional attachment sites between the endothelial cell and the subcellular matrix, exposure to hypertonic solutions caused a biphasic increase in Lp (Kajimura et al. 1997). The simplest interpretation of these experiments was that a reduction in endothelial cell volume resulted in a change in the geometry of the principal water pathway across the capillary to increase permeability only when the attachment of the endothelial cell to the basement membrane was compromised. The mechanisms whereby EC-ECM attachment modulates microvessel permeability are not well understood. One possibility is that, in the presence of decreased attachment of the endothelial cell to the basement membrane, a reduction in the volume of endothelial cells directly modifies the resistance to water flow through the junction between cells by widening the junction or reducing the length of the junction overlap. A second possibility is that changes in endothelial cell attachment modify the way the endothelial cells respond to applied forces (in this case, a change in cell volume). We expected that the second possibility may Journal of Physiology (1999) 1. We tested whether calcium (Ca¥)-dependent mechanisms were essential for our previous observation that a change in the endothelial cell (EC)-extracellular matrix (ECM) attachment caused an increase in microvessel hydraulic permeability (Lp) after exposure to hypertonic solutions in single perfused mesenteric microvessels in pithed frogs (Rana pipiens)., 518.1, pp. 227-238 227 Endothelial cell shrinkage increases permeability through a Ca¥-dependent pathway in single frog mesenteric2. In microvessels where integrin-dependent EC-ECM attachments were disrupted by pretreatment with the peptide Gly-Arg-Gly-Asp-Thr-Pro (GRGDTP; 0·3 mmol l¢), we measured microvessel Lp after exposure to hypertonic solutions under experimental conditions that reduced Ca¥ influx into endothelial cells. 3. High K¤ solutions (59·7 and 100 mmol l¢ K¤) were used to depolarize the endothelial membrane and therefore to reduce the electrochemical driving force for Ca¥ influx through conductive Ca¥ channels. These solutions abolished the increase in Lp caused by hypertonic solutions in the microvessels pretreated with GRGDTP. 4. We previously suggested that t...

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Effect of Hypertonic Saline Pre-treatment on Ischemia–Reperfusion Lung Injury in Pig

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Albumin impacts the effects of tonicity on microvascular hydraulic permeability1

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