Oxidized LDL and lipoprotein(a) stimulate renin release of juxtaglomerular cells

Abstract

Atherogenic lipoproteins accumulate in the arterial wall and may potentially stimulate neighboring cells. In the glomerulus the vascular pole resembles afferent arteries in close vicinity to the juxtaglomerular apparatus. We examined the effects of native and oxidized LDL and lipoprotein(a) [Lp(a)] on renin release of juxtaglomerular cells (JG cells) prepared in primary culture from mouse kidneys. Renin activity of JG cells was measured in culture supernatants and cells between the 20th and 40th hour of culturing. Spontaneous renin release into the cell supernatant was 26 +/- 1% of total activity. Control stimulation of JG cells by melittin or forskolin dose-dependently increased renin release up to 90 +/- 2%. Incubation of JG cells with native LDL (50 and 300 micrograms/ml) or native Lp(a) (30 micrograms/ml) did not alter renin release. Oxidized LDL increased renin release to 34 +/- 1% and 43 +/- 1% at 50 and 300 micrograms/ml, while oxidized Lp(a) stimulated renin release to 33 +/- 1%, 42 +/- 1%, and 71 +/- 2% at 1, 10, and 30 micrograms/ml, respectively. Coincubation with superoxide dismutase and catalase, enzymes removing O2- and H2O2, completely eliminated oxidized LDL and Lp(a)-stimulated renin release. In the absence of lipoproteins, renin release was significantly stimulated by activation of O2- formation by the xanthine/xanthine oxidase reaction. These data indicate that oxidized LDL and Lp(a) stimulate renin release in JG cells by a mechanism involving oxygen-derived radicals. Thus, oxidatively modified atherogenic lipoproteins may contribute to renin-dependent hypertension in renoparenchymatous kidney disease.