Utilizing cocultures of mouse renal juxtaglomerular cells with bovine microvascular endothelial cells, we have examined whether endothelial cells exert direct influence on renin secretion from renal juxtaglomerular cells.In the presence of endothelial cells both spontaneous and forskolin (10 isM) or isoproterenol (10 sM) stimulated renin release were markedly attenuated. The stimulatory effect ofthe calmodulin antagonist calmidazolium (10 pM) on renin secretion was not altered by endothelial cells, whereas the stimulatory effect of ethylisopropylamiloride (50 pM) an inhibitor of sodium-proton exchange was enhanced in the presence of endothelial cells. Indomethacin (10 1M) and NG-monomethyl-l-arginine (NMMA) (1 mM) used to inhibit cyclooxygenase activity and production of endothelium-derived relaxing factor (EDRF) decreased spontaneous renin release in the presence of endothelial cells only, but had no effect on forskolin stimulated

Macrophages have been described to release nitric oxide (NO) as a cytotoxic radical. This highly unstable substance is as well known as endothelium-derived relaxing factor produced by vascular endothelial cells. Because of its cytotoxic activity the synthesis of NO by rat Kupffer cells, the liver macrophages, upon stimulation with endotoxin (lipopolysaccharide; LPS) and tumor necrosis factor-α (TNF-α) in combination with prostaglandin E₂ (PGE₂) and dibutyryl cAMP (dBcAMP) was studied. Kupffer cells were stimulated after 48 h of primary culture. NO was quantified as NO₂ in the cell medium 24 h after stimulation. LPS stimulated NO generation 5- to 10-fold over the basal level. This increase could be further enhanced by PGE₂ and dBcAMP, especially when added 1 h after LPS. NO generation after stimulation with LPS or LPS + PGE₂ depended on the simultaneous production of PGE₂ by the stimulated Kupffer cells. It could be partly inhibited by anti-PGE₂ antibody or acetylsalicylic acid. While murine TNF-α did not stimulate NO synthesis significantly, added PGE₂ raised NO synthesis about 6-fold. The addition of dBcAMP to TNF-α in the same concentration as with LPS, however, had no effect. Thus, stimulation by LPS + PGE₂ equals that of LPS + dBcAMP whereas TNF-α + PGE₂ does not equal TNF-α + dBcAMP, indicating differences in the mode of action of PGE₂ on LPS- or TNF-α-treated Kupffer cells.

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