[Role of neutral endopeptidases in capillary dysfunctions of diabetic origin in rats]

Among numerous complications associated with diabetes, the alterations of the normal properties of various microcirculation circuits lead to important dysfunctions which may contribute to target organ damage. As the endothelium plays a crucial role in the microcirculatory circuits, it is suggested that diabetes may influence both the physical and endocrine properties of that cell layer. In 1995, we reported an important increase in plasma extravasation in a model of diabetes in rats treated with streptozotocin. The increase of plasma extravasation was particularly significant in the pulmonary, skin and splanchnic areas. In that particular study, it was of interest that inhibitors of neutral endopeptidases, such as thiorphan, phosphoramidon and SQ 28,603 (specific inhibitor of the recombinant neutral endopeptidases2) corrected almost completely the increase of plasma extravasation induced by diabetes when compared with control rats. It is also worthy of note that the three above-mentioned inhibitors failed to normalize in any case the hyperglycaemia associated with the diabetes in these animals. The present document is a summary synthesis of the putative role of neutral endopeptidases and of the beneficial effects of the inhibitors of these enzymes in diabetes-induced plasma extravasation in the rat.