In this application, the applicant proposes to study the effects of adenosine and other vasoactive compounds on the capillary endothelial glycocalyx. Recent work has shown the glycocalyx to be a thick layer of proteoglycans and glycoproteins that lines the endothelial vascular space and appears to be the true interface between the blood and the vascular cells. The layer has been proposed to play a role in vascular permeability, hemostasis and capillary tube hematocrit. Previous work in this lab showed that TNF-alpha (known to be released from mast cells) causes increased glycocalyx permeability. We hypothesize that adenosine will increase the permeability of FITC-dextran 70 into the glycocalyx, through degranulation of mast cells via the A3 adenosine receptors. The goals of this work are to elucidate the effects of varying doses of adenosine receptor. The goals of this work are to elucidate the effects of varying doses of adenosine (and other vasodilators) on glycocalyx permeability and thickness, compare this effect to that elicited by other vasoactive agents which act either through mast cells or independent of mast cells, and evaluate the role of the A3 adenosine receptor in this response using A3 knockout mice as well as other state of the art techniques. We believe and the endothelial glycocalyx will provide to be an important regulator of many vascular processes.
| Platts, Steven H; Duling, Brian R (2004) Adenosine A3 receptor activation modulates the capillary endothelial glycocalyx. Circ Res 94:77-82 |
