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Thrombin increases permeability only in venules exposed to inflammatory conditions
F E Curry1, M Zeng, R H Adamson
1Department of Human Physiology, University of California, Davis, 1 Shields Ave., Davis, CA 95616, USA. fecurry@ucdavis.edu
Summary
Rat venules do not acutely respond to thrombin. However, after prior injury, venules demonstrate increased hydraulic conductivity (Lp) when exposed to thrombin 24 hours later, indicating altered endothelial cell response.
Area of Science:
- Vascular biology
- Endothelial cell physiology
- Inflammation research
Background:
- Thrombin is commonly used to model acute inflammatory responses in cultured endothelial cells.
- Preliminary studies suggested rat mesenteric venules do not exhibit acute responses to thrombin.
Purpose of the Study:
- To investigate if prior endothelial injury modifies the response of rat venules to thrombin.
- To test the hypothesis that venules respond to thrombin 24 hours post-injury.
Main Methods:
- Measurement of hydraulic conductivity (Lp) in rat mesenteric venules.
- Microperfusion of venules with rat thrombin (10 U/ml) at different time points after initial vehicle control perfusion.
- Comparison of Lp before and after thrombin exposure at acute (within 2 hours) and delayed (24-27 hours) intervals.
Main Results:
- No significant increase in Lp was observed when venules were exposed to thrombin acutely (within 2 hours) post-injury.
- A significant, transient increase in Lp was observed in all venules perfused with thrombin 24-27 hours after initial injury.
- Peak Lp on day 2 reached 24 +/- 4.2 x 10(-7) cm.s-1.cmH2O-1.
Conclusions:
- Prior endothelial injury alters the endothelial cell phenotype, leading to a delayed but significant response to thrombin.
- Endothelial cell phenotypic plasticity is crucial for regulating permeability in intact venules following inflammatory events.
- Localized leaky sites may form in venules subsequent to prior inflammatory responses.