Atherogenic lipoproteins and reactive oxygen species stimulate renin release from isolated juxtaglomerular (JG) cells. Here we assessed whether stimulation of renin release is mediated by formation of superoxide anion (O2-), and whether the effects of oxidized lipoproteins, like in many other biological systems, can be prevented by the antiatherogenic high density lipoprotein (HDL). Lipoproteins were prepared from human plasma, and JG cells from mouse and rat kidneys. Basal renal activity of JG cells was measured in culture supernatants and cells, and was dose-dependently and significantly stimulated by oxidized LDL (50 and 300 micrograms/ml) and by oxidized Lp(a) (1, 10 and 30 micrograms/ml). Administration of HDL alone had no effect on renin release. However, coincubation with 100 micrograms/ml HDL significantly suppressed oxidized LDL- and oxidized Lp(a)-stimulated renin release. O2- production of JG cells was directly measured using a chemiluminescence assay. Stimulation with 10 micrograms/ml oxidized LDL and oxidized Lp(a) significantly increased the O2- generation of JG cells. In the presence of 5 micrograms/mL HDL, O2- production was reduced to control levels. These data indicate that stimulation of JG cells with oxidized LDL and Lp(a) induces formation of O2-, which may stimulate renin release in an autocrine fashion. Renin release can be prevented by HDL, presumably by preventing the formation of O2-.