Effect of extreme elevations in venous pressure on reflection coefficient in the lung.
Animals; Blood Pressure/*physiology; Blood Proteins/analysis; Capillary Permeability/*physiology; Dogs; Endothelium; Female; Forelimb/physiology; Hematocrit; In Vitro Techniques; Lung/*drug effects/physiology; Male; Perfusion; Pulmonary Veins/*physiology; Solvents/*chemistry; Vascular/*drug effects
We determined whether the solvent drag reflection coefficient (sigma f) for total proteins of a canine perfused left lower lung lobe (LLL) preparation decreases at elevated venous pressures (Pv). We found that sigma f (estimated using the hematocrit-protein technique) remained constant at all Pv's (30-95 mm Hg) evaluated. These results were unanticipated, since previous studies reported increases in protein permeability at Pv's within this range. We conducted two additional studies to better understand the basis for these observations. In the first, we evaluated the effect of high Pv (85 mm Hg) on sigma f of a canine perfused forelimb preparation and found sigma f to be reduced. This difference in response suggests that the normal sigma f's observed in the LLL were not due to high Pv per se, but rather that there is some intrinsic difference between the pulmonary and the systemic circulations that accounts for the difference. The second study was designed to determine whether the normal sigma f's observed in the LLL at high Pv's provide meaningful information about pulmonary vascular endothelial permeability. We damaged LLL's with alloxan, oleic acid, or HCl and obtained near normal estimates of sigma f at high Pv. These results indicated that it is not possible to easily distinguish between a normal and a damaged pulmonary vasculature when sigma f is measured at high Pv. We suggest that the normal estimates of sigma f obtained at high Pv in the LLL results from an increased fraction of the transvascular flow occurring through pathways that exclude macromolecules.
Maron M B; Lang S A
Microvascular research
1992
1992-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0026-2862(92)90006-b" target="_blank" rel="noreferrer noopener">10.1016/0026-2862(92)90006-b</a>
Primary cilia regulates the directional migration and barrier integrity of endothelial cells through the modulation of hsp27 dependent actin cytoskeletal organization.
*Cell Movement; Actin Cytoskeleton/*metabolism; Animals; Blotting; Capillary Permeability/*physiology; Cell Adhesion; Cilia/metabolism; Endothelial Cells/cytology/*metabolism; Fluorescent Antibody Technique; Focal Adhesions/metabolism; HSP27 Heat-Shock Proteins/*metabolism; Mice; Polycystic Kidney Diseases/physiopathology; Signal Transduction/physiology; Transgenic; Western
Cilia are mechanosensing organelles that communicate extracellular signals into intracellular responses. Altered functions of primary cilia play a key role in the development of various diseases including polycystic kidney disease. Here, we show that endothelial cells from the oak ridge polycystic kidney (Tg737(orpk/orpk) ) mouse, with impaired cilia assembly, exhibit a reduction in the actin stress fibers and focal adhesions compared to wild-type (WT). In contrast, endothelial cells from polycystin-1 deficient mice (pkd1(null/null) ), with impaired cilia function, display robust stress fibers, and focal adhesion assembly. We found that the Tg737(orpk/orpk) cells exhibit impaired directional migration and endothelial cell monolayer permeability compared to the WT and pkd1(null/null) cells. Finally, we found that the expression of heat shock protein 27 (hsp27) and the phosphorylation of focal adhesion kinase (FAK) are downregulated in the Tg737(orpk/orpk) cells and overexpression of hsp27 restored both FAK phosphorylation and cell migration. Taken together, these results demonstrate that disruption of the primary cilia structure or function compromises the endothelium through the suppression of hsp27 dependent actin organization and focal adhesion formation, which may contribute to the vascular dysfunction in ciliopathies.
Jones Thomas J; Adapala Ravi K; Geldenhuys Werner J; Bursley Chris; AbouAlaiwi Wissam A; Nauli Surya M; Thodeti Charles K
Journal of cellular physiology
2012
2012-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/jcp.22704" target="_blank" rel="noreferrer noopener">10.1002/jcp.22704</a>