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The cellular distribution of angiotensin II type 1 (AT1) and type 2 (AT2) receptor mRNA was examined in mouse kidneys at several embryonic stages (12 to 18 days; 19 days = full term) and up to three weeks after birth by in situ hybridization. The expression of both AT1 and AT2 mRNAs appeared simultaneously at 14 days of gestation. However, their distributions were contrasting: AT1 mRNA was expressed in mature glomeruli and maturing S-shaped bodies throughout the stages examined. AT1 expression was also detected at 16 days of gestation in the proximal and distal tubules and peaked at the end of gestation. Both the temporal and spatial expression of AT1 coincide with the differentiation and proliferation of glomerular mesangial and tubular cells during nephrogenesis. In contrast, AT2 mRNA was present only in the mesenchymal cells adjacent to the stalk of the ureter bud at early developmental stages, and, later, extended to the mesenchymal cells located near, but outside, the nephrogenic area of superficial cortex and also the cells between collecting ducts. AT2 expression in these regions decreased markedly within three weeks after birth. Temporally and spatially, AT2 mRNA expression coincides with the epithelial-mesenchymal interactions that take place during early phases of nephrogenesis. The site of AT2 expression also overlaps closely with that of a specific group of cells which undergo apoptosis following nephrogenesis. Thus, contrary to current belief, the activation of AT1 and AT2 genes takes place in different cell types of the kidney during embryonic development, and thereby conceivably contributes to the ontogeny of those specific renal cells.

SummaryUrokinase immobilized polymer is highly antithrombotic, which cannot be explained only by fibrinolysis. We immobllized 10 IU/cm2 of urokinase to polyurethane by using maleic anhydride methylvinyl ether copolymer as a carrier. Then we incubated blood in circular tubes made of this material, measured the clotting factors and observed the surface of the tubes after incubation by scanning electronmicroscopy and immunofluorescence microscopy. After 5 min incubation, the relative activities of factors V, VIII, IX, X and XII, fibrinogeil, plasminogen and α2 plasmin inhibitor decreased, but the activity of factor VII increased. No platelet adhesion to the surface of the urokinase immobilized polyurethane was observed and there was no significant adsorption of serum proteins, including fibrinogen, fibronectin and vWF antigen, or the surface. Urokinase-immobilized polyurethane catalyzed the digestion of clotting factors as well as fibrinolysis and also inhibited platelet adhesion on its surface probably by inhibiting protein adsorption and its clinical application including vessel prosthesis should be developed further.

Upon exposure to a transient ischemia, the distal tubule of the kidney often escapes the severe damage which afflicts the proximal tubule. To ascertain whether this feature of the distal tubule is attributable to its intrinsic cellular properties, we focused on two pairs of unique tubule segments; distal versus proximal convoluted tubules in the superficial cortex and distal versus proximal straight tubules in the outer stripe of the outer medulla. These tubules were chosen because, firstly, they can be identified by morphology and immunostaining, and secondly, each pair has the same anatomical relationship to the circulation. Detailed morphometric analyses were performed six hours following unilateral transient ischemia in adult rats to semiquantitate the local tissue damage in these specific nephron segments. The architecture of the distal convoluted and straight tubules was remarkably well preserved, contrasting to the moderate to extensive necrotic changes seen in the proximal tubules. In search of the potential intrinsic cellular mechanism that underlies the observed difference, we examined the segmental distribution along the nephron of manganese superoxide dismutase gene transcripts by in situ hybridization. This antioxidant enzyme gene was expressed primarily in the distal tubules with contrastingly low levels of expression in the proximal tubules. Moreover, following ischemia-reperfusion, this distal tubule-dominant pattern was further accentuated immediately following reperfusion. The study indicates that the marked difference between the proximal and distal tubules in their susceptibility to injury in vivo is attributable to their intrinsic cellular properties, which include the local level of antioxidants.

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