The physical and chemical nature of the pathways for macromolecule exchange when the permeability of microvessels is increased remains poorly understood.
The specific aims of the proposed research are to investigate three hypotheses which describe the transport mechanisms responsible for increased macromolecule exchange in post-capillary venules. The first hypothesis states that passive diffusive and convective transport through porous pathways are the principal mechanisms whereby water and macromolecules cross the capillary wall during high permeability states. The second hypothesis states that the area for exchange and the length of the pathway for water and solute exchange across microvessels are modulated via changes in the size and shape of endothelial cells in the region of the intercellular junctions. The third hypothesis states that the frictional resistance to water and solute movement through porous intercellular pathways during altered permeability is determined by networks of fibrous molecules associated with the basement membrane and edothelial cell surface. These hypotheses are an extension of the concepts developed during the current funding period. To test the hypotheses the investigators will use methods developed in their laboratory to cannulate and perfuse individual microvessels and to measure the premeability coefficients of their walls to fluorescently labelled macromolecular solutes. An important part of the research plan is to investigate premeability properties in mammalian post- capillary venules. Permeability will be increased in a graded manner using the calcium ionophore A23187 and by using inflammatory mediators. The ultrastructure of microvessels in the segment used to measure permeability will also be examined to correlate structure and function. The investigations provide a direct experimental route to further understanding of the mechanisms which modulate capillary permeability during high permeability states leading to edema.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL028607-09
Application #
3339967
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1982-07-01
Project End
1992-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
9
Fiscal Year
1990
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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