INTERLEUKIN-1-BETA INDUCES THE FORMATION OF NITRIC-OXIDE IN ISOLATED JUXTAGLOMERULAR CELLS - INFLUENCE ON RENIN SECRETION

Renin secretion may be modulated by nitric oxide (NO). We studied whether interleukin-1 beta (IL-1 beta) induces endogenous NO synthesis in mouse juxtaglomerular cells (JGC) in primary culture, and whether endogenous NO or NO applied exogenously via sodium nitroprusside (SNP) influences renin secretion. JGC seeded on culture plates were stimulated by IL-1 beta or by SNP. Cyclic guanosine 3',5'-monophosphate (cGMP) in the cell supernatant was determined as indicator for NO effects. Stimulation of JGC with IL-1 beta or SNP increased cGMP in the supernatant significantly. The NO synthase inhibitors N-G-nitro-L-arginine or N-G-monomethyl-L-arginine, or the NO scavenger oxyhaemoglobin prevented the IL-1 beta-induced increase of cGMP. The biological activity of NO was shown in a bioassay by the vasodilatory effect of the effluent from an IL-1 beta-stimulated JGC column on a precontracted rat aortic ring and was prevented by oxyhaemoglobin and methylene blue. Renin activity of JGC was detected in the culture supernatants and the cells. Spontaneous renin secretion into the cell supernatant was 26 +/- 1% of total activity. Melittin or forskolin concentration dependently increased renin secretion up to 90 +/- 2%. Incubation of JGC with IL-1 beta in the absence or presence of NO inhibitors did not alter spontaneous or stimulated renin secretion. SNP (30 mu M) had a dual effect on renin secretion. After 1 h of incubation, it inhibited basal renin secretion, whilst it had a stimulatory effect after 20 h of incubation. Melittin- or forskolin-stimulated renin secretion was not influenced by SNP. In summary, IL-1 beta stimulates NO synthesis in JGC. Endogenous NO was without influence on renin secretion, whereas high concentrations of exogeneously applied NO had a dual effect on renin secretion.