The physical and chemical nature of the principal pathway(s) for water and hydrophilic solutes across the capillary wall remains poorly understood.
The specific aims of the proposed research are to investigate two hypotheses describing mechanisms of water flow and solute diffusion and exclusion in the transcapillary pathways. One states that a network of fibrous molecules on the endothelial cell surface is the principal determinant of the permeability and selectivity of the capillary wall. The second hypothesis states that the plasma proteins interact with the fiber matrix to maintain the normal permeability properties of the capillary wall. To test these hypotheses we will use methods developed in our laboratory to measure the permeability properties of the walls of individually perfused capillary blood vessels. The hydraulic conductivity will be measured using a modified Landis microocclusion technique. A microscope photometer will be used to measure the permeability coefficients to colored hydrophilic solutes with molecular weights between 2000 and 20,000 and a range of shape and charge of physiological pH. We will seek an internally consistent description of the measured permeability properties in terms of the fiber radius and volume of a fiber matrix within the transcapillary pathways. The investigations provide a direct experimental route to further understanding of the mechanisms which maintain, and possibly regulate, vascular permeability. They will also lead towards a better understanding of the relation between changes in blook composition and abnormalities of vascular wall structure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL028607-04
Application #
3339963
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1982-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
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Curry, Fitz-Roy E; Clark, Joyce F; Jiang, Yanyan et al. (2016) The role of atrial natriuretic peptide to attenuate inflammation in a mouse skin wound and individually perfused rat mesenteric microvessels. Physiol Rep 4:
Morikis, Vasilios A; Radecke, Chris; Jiang, Yanyan et al. (2016) Atrial natriuretic peptide down-regulates neutrophil recruitment on inflamed endothelium by reducing cell deformability and resistance to detachment force. Biorheology 53:109
Zhang, Lin; Zeng, Min; Fan, Jie et al. (2016) Sphingosine-1-phosphate Maintains Normal Vascular Permeability by Preserving Endothelial Surface Glycocalyx in Intact Microvessels. Microcirculation 23:301-10
Morikis, Vasilios A; Radecke, Chris; Jiang, Yanyan et al. (2015) Atrial natriuretic peptide down-regulates neutrophil recruitment on inflamed endothelium by reducing cell deformability and resistance to detachment force. Biorheology 52:447-63
Curry, Fitz-Roy E; Clark, Joyce F; Adamson, Roger H (2015) Microperfusion Technique to Investigate Regulation of Microvessel Permeability in Rat Mesentery. J Vis Exp :
Adamson, R H; Clark, J F; Radeva, M et al. (2014) Albumin modulates S1P delivery from red blood cells in perfused microvessels: mechanism of the protein effect. Am J Physiol Heart Circ Physiol 306:H1011-7
Zeng, Ye; Adamson, Roger H; Curry, Fitz-Roy E et al. (2014) Sphingosine-1-phosphate protects endothelial glycocalyx by inhibiting syndecan-1 shedding. Am J Physiol Heart Circ Physiol 306:H363-72
Tarbell, John M; Simon, Scott I; Curry, Fitz-Roy E (2014) Mechanosensing at the vascular interface. Annu Rev Biomed Eng 16:505-32
Adamson, R H; Sarai, R K; Altangerel, A et al. (2013) Microvascular permeability to water is independent of shear stress, but dependent on flow direction. Am J Physiol Heart Circ Physiol 304:H1077-84

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