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Interendothelial junctions of cardiac capillaries in rats: their structure and permeability properties
B J Ward1, K F Bauman, J A Firth
1Department of Anatomy, St. George's Hospital Medical School, London, UK.
Insights
Rat cardiac capillaries restrict large molecules like haemoglobin and catalase but allow smaller ones like cytochrome C to pass through intercellular spaces. These spaces act as size-selective sieves, influencing macromolecule permeability.
Area of Science:
- Cardiovascular Biology
- Endothelial Cell Biology
- Capillary Permeability
Background:
- Understanding cardiac capillary structure is crucial for drug delivery and understanding tissue homeostasis.
- The permeability of capillaries to macromolecules influences physiological and pathological processes.
Purpose of the Study:
- To investigate the structural basis of rat cardiac capillary permeability to macromolecules of varying sizes.
- To elucidate the role of intercellular spaces and endothelial cell junctions in macromolecule passage.
Main Methods:
- Isolated perfused rat heart model.
- Electron microscopy with tracer molecules (haemoglobin, catalase, cytochrome C, horseradish peroxidase).
- Analysis of intercellular gap dimensions using advanced imaging techniques.
Main Results:
- Haemoglobin (6.4 nm) and catalase (10.4 nm) were retained on the luminal side of the endothelium.
- Cytochrome C (3 nm) and horseradish peroxidase (6 nm) traversed the endothelium into the subendothelial space.
- Intercellular gaps, particularly zonular regions (5.4 nm), demonstrated size-selective filtration of macromolecules.
Conclusions:
- Rat cardiac capillaries possess size-selective barriers within their intercellular spaces.
- These structural features, specifically narrow intercellular gaps, play a significant role in regulating macromolecule permeability.
- While size is a key factor, other permeability determinants may also be involved.
Abstract:
The isolated perfused heart model was used to examine the structure of rat cardiac capillaries and their permeability to macromolecules of various sizes. Haemoglobin (diameter 6.4 nm) and catalase (10.4 nm) did not cross the endothelium but remained on the luminal side. Cytochrome C (3 nm) and horseradish peroxidase (6 nm) both crossed the endothelium to the subendothelial space and filled the caveolae on the abluminal side as well as the entire length of the lateral intercellular spaces. The membranes of the endothelial cells are separated by an intercellular gap of mean width 18.2 nm. At one or more zonular regions within each lateral intercellular space the two membranes approach each other more closely and frequently appear to fuse. However, tilting the specimen shows that, in these regions, there is a gap of mean width 5.4 nm (in lanthanum- and tannic acid-treated tissue, 3.8 nm in ferrocyanide-treated tissue) between the membranes. We conclude that these narrow regions sieve macromolecules on the basis of size although other factors may determine their permeability properties.