INCREASED GLOMERULAR NITRIC-OXIDE SYNTHESIS IN GENTAMICIN-INDUCED RENAL-FAILURE

Renal glomeruli isolated from normal rats and from rats with gentamicin-induced renal failure were incubated with substances that modify nitric oxide (NO) synthesis and the resulting changes in glomerular cyclic GMP (cGMP) levels were measured by radioimmunoassay. Glomeruli from normal and gentamicin-treated rats contained 0.17 +/- 0.04 and 2.02 +/- 0.63 pmol cGMP/mg protein respectively. In normal glomeruli, acetylcholine and bradykinin significantly increased cGMP levels whereas N-G-nitro-L-arginine-methyl ester, an inhibitor of NO synthesis, completely blocked this increase. In glomeruli from gentamicin-treated animals, acetylcholine and bradykinin also stimulated cGMP accumulation, while N-G-nitro-L-arginine-methyl ester decreased the cGMP content to levels significantly below the basal concentrations. These data suggest an increased glomerular production of NO in rats with gentamicin-induced renal failure.