Active renin plays an important role in regulating both salt and fluid homeostasis in the body and is exclusively secreted into the circulatory system by the renal juxtaglomerular epitheloid cells (JG-cells). It is well established that an increase of cAMP in JG-cells stimulates renin release and that increased Ca²⁺-concentrations are paralleled by inhibition of release. This stands in contrast to classical secretion processes, in which exocytosis is stimulated by Ca²⁺, meaning that the secretion mechanisms in renin producing cells remain largely obscure. The aim of our work is to analyze the behavior of renin storage vesicles under conditions stimulating or inhibiting renin secretion in order to throw light on the mechanisms responsible for renin vesicle exocytosis. For this purpose we have analyzed the shape and structure of renin storage vesicles under different secretion stimulating maneuvers.

For this aim we have perfused kidneys of 129SV mice with a solution containing isoproterenol to stimulate renin secretion via a high intracellular cAMP concentration. Occasionally, we further increased the stimulating effect by adding EGTA to the perfusion solution and thereby decreasing intracellular concentration of calcium ions. The structure of renin storage vesicles was analyzed by 3-dimensional electron-microscopical reconstruction of single JG-cells with corresponding secretory vesicles. Reconstructions were made with 70nm thick serial slices of kidney tissue. Slices were photographed using electron microscopy and reconstructed with the AMIRA program.

In renin cells stimulated only with isoproterenol for 3 minutes, we so far found no visible exocytotic events. Some, but not all of the renin containing vesicels appear to be interconnected to mesh-like structures. In JG-cells stimulated for 10 minutes with isoproterenol and EGTA, we found some exocytotic events. Here, in addition to normal exocytotic vesicles, some vesicles appear to be less electron-dense. In JG-cells stimulated for 15 minutes with isoproterenol and EGTA over a sustained time period, most of the renin containing vesicles show a low electron density. These vesicles are interconnected to each other, forming a cavern-like structure.

In conclusion, single exocytotic events seem to be very rare in renin cells, because they were observed only upon strong stimulation. Moreover, in JG-cells stimulated for 15 minutes the renin pool appears to be depleted. Nearly all vesicles showed a low electron densitiy, which almost certainly means that they are renin-free. The fact that these vesicles form a single cavern-like structure could point to the so-called "compound-exocytosis" mechanism. According to this theory, vesicles first fuse homotypically with each other forming a mesh-like compound, which then fuses with the cell membrane. This could also be an explanation for the rarity of exocytotic events.