The aim of the present study was to assess the role of endothelin (ET) in ischemia-reperfusion (I/R)-induced mucosal injury. Mucosal permeability ((51)Cr-EDTA clearance) and tissue myeloperoxidase (MPO) activity were significantly increased after 30 min of ischemia followed by 30 min of reperfusion. The I/R-induced increases in mucosal permeability and polymorphonuclear leukocyte (PMN) infiltration were significantly attenuated by pretreatments with ET(A) (BQ-485) and/or ET(B) (BQ-788) receptor antagonists. Monoclonal antibody (MAb) directed against intercellular adhesion molecule-1 (ICAM-1; MAb 1A29) and superoxide dismutase (SOD) pretreatments significantly attenuated the increased mucosal permeability and PMN infiltration in a similar manner as with ET receptor antagonists. Superior mesenteric artery blood flow was significantly reduced during the reperfusion period. Both ET receptor antagonists caused a significant rise in blood flow compared with an untreated I/R group. In conclusion, our data suggest that ET(A) and/or ET(B) receptors, ICAM-1, and superoxide play an important role in I/R-induced mucosal dysfunction and PMN infiltration. Furthermore, ET is involved in the pathogenesis of post-reperfusion-induced damage and beneficial effects of ET receptor antagonism are related to an improvement of disturbed blood flow during the reperfusion period.

To overcome the deficiencies of previous findings, the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) were studied at very short age intervals to allow a more precise definition of the shape and timing of their developmental curves in normal, hypothyroid and underfed rats. In addition, AchE expression in developing cerebellum was studied histochemically in these three neurological models. When compared with structural findings in the literature, the results provide the following information on the normal and abnormal developing cholinergic system, related or not to cerebellar neurotransmission (1) AchE activity, unlike ChAT, can be considered as a good marker of the developing cholinergic archicerebellum. (2) ChAT and AchE are transiently expressed together in functionally noncholinergic Purkinje cells. In contrast with most regions of the central nervous system, the high ratio of ChAT to AchE activities in the early stage of cerebellar development suggests an enhanced synthesis of acetylcholine (Ach). The level of ChAT activity correlates with Purkinje cell size, supporting the concept of a neurotrophic role of Ach in early maturing macroneurons. (3) The archicerebellar cholinergic network appears to be relatively well preserved from undernutrition and, to an even greater extent, from hypothyroidism, compared to other systems of neurotransmission formed later and more widely distributed throughout the cerebellum. The presynaptic compartment seems to be more affected than the postsynaptic compartment. (4) In disagreement with some data in the literature, the abnormalities induced by both abnormal thyroidal and nutritional states were found to be irreversible.

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