Blockade of endothelin-A receptors but not endothelin-B receptors reduces capillary leakage in acute pancreatitis

We have previously shown that blockade of endothelin (ET) stabilizes (incre ased) capillary permeability in severe acute pancreatitis (AP). The present study evaluates whether this is a specific effect of endothelin-A or endot helin-B receptor blockade. The experiments demonstrate that ET-A receptor b lockade significantly reduces capillary permeability in the colonic mucosa in rats with severe AP, while having no effect in healthy control animals. In contrast, ET-B-receptor blockade increases permeability in healthy anima ls, in AP it has no effect. The results allow for the following conclusions : (1) The endothelin system plays an important role in regulating capillary permeability; (2) in severe acute pancreatitis capillary leakage can effec tively be treated by blocking endothelin-A, but not ET-B receptors,which ma y explain different results reported for different (non-selective) ET antag onists. (3) Further characterization of the ET-system, factors activating E T and agents (selectively) blocking ET receptors is necessary to better und erstand to role of ET in regulating capillary permeability.