Thrombin increases permeability only in venules exposed to inflammatory conditions.
Thrombin is widely used to stimulate a variety of responses in cultured endothelial cell monolayers as a model of acute vascular endothelial response to inflammatory mediators. However, preliminary results indicated that rat mesenteric venules did not respond acutely to thrombin. We tested the hypothesis that rat venules would respond to thrombin 24 h after prior injury by microperfusion. Vessel responsiveness was measured as hydraulic conductivity (Lp). When venules were exposed to rat thrombin (10 U/ml) within 2 h of initial perfusion with vehicle control, there was no increase in Lp of any vessel from a mean baseline of 1.2 +/- 0.2 x 10(-7) cm.s-1.cmH2O-1. In contrast, when perfused with thrombin at 25-27 h after initial perfusion, every venule responded to thrombin with a transient increase in Lp. The mean peak Lp on day 2 in response to thrombin was 24 +/- 4.2 x 10(-7) cm.s-1.cmH2O-1. Our results suggest that prior endothelial injury modifies the endothelial cell phenotype and alters the response of endothelial cells to thrombin after 24 h. Phenotypic plasticity of endothelial cells may play a key role in the regulation of permeability of some endothelial cells in culture and in intact venules, where localized leaky sites may form where there had been a previous inflammatory response.
Curry
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FE
Department of Human Physiology, University of California, Davis, 1 Shields Ave., Davis, CA 95616, USA. fecurry@ucdavis.edu
Zeng
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Adamson
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D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000276:immunology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology*; D006490:Hemostatics / Q000494:pharmacology*; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000494:pharmacology*; D014657:Vasculitis / Q000503:physiopathology; D014699:Venules / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D006490:Hemostatics; D010972:Platelet Activating Factor; D013917:Thrombin