The role of microcirculation in the pathogenesis and course of chronic
inflammatory bowel disease is still unclear. The aim of this study was the evaluation of the role of microcirculation in
colitis activity in the rat TNBS (
trinitrobenzenesulfonic acid)
colitis model using
endothelin-1 and a selective
endothelin-1 receptor antagonist (LU-135252). Target parameters were capillary blood flow, functional capillary density, vascular permeability, and leukocyte sticking as well as recording of hematocrit, weight course, diuresis, stool quality, and degree of
inflammation using a histological
colitis score. The acute phase of TNBS
colitis is characterized by an extensive disturbance of microcirculation (a significant decrease in capillary blood flow and capillary density and a significant increase in capillary permeability and leukocyte sticking in the mucosa). There is also a significant increase in hematocrit and a significant decrease in diuresis and weight. An exogenous supply of
endothelin-1 does not lead to an aggravation of these disorders because of a possible blockage of the
endothelin-1 receptors by endogenous
endothelin-1 in this florid inflammatory phase. Applying the selective
endothelin-1 receptor A antagonist
LU-135252 leads to a significant improvement of all microcirculatory parameters and clinical findings compared to the untreated
colitis group. Direct improvement of capillary blood flow in the early phase of
colitis leads to reduced
colitis activity, which underscores the pathogenetic role of the microcirculation in the progression of
colitis.