GENTAMICIN TREATMENT INCREASES MESANGIAL CELL NITRIC-OXIDE PRODUCTION

Gentamicin-induced decreases in glomerular filtration rate have been a ssociated with a marked decline in the glomerular capillary ultrafiltr ation coefficient which could be mediated by mesangial cell contractio n. We have assessed a possible role of endogenous nitric oxide (NO) as a modulator of the proliferative and contractile effects of gentamici n on mesangial cells. NO synthesis and release, measured as nitrite pr oduction, were increased in the presence of gentamicin; this increase was blocked by coincubation with L-NAME. Mesangial cells treated with gentamicin, but not cells under control conditions, expressed mac-iNOS mRNA and presented positive immunoreactivity for mac-iNOS. Gentamicin induced a reduction of the planar surface area of cultured rat mesang ial cells; cell treatment with gentamicin plus L-arginine significantl y decreased the contractile effect of gentamicin. Gentamicin increased both [H-3]thymidine incorporation into DNA and viable cell number; wh en L-arginine was added together with gentamicin, this abolished the e ffect of gentamicin on mesangial cell proliferation. The present studi es demonstrate that gentamicin induces the expression of mac-iNOS and produces contraction and proliferation in mesangial cells. These actio ns seem to be modulated by mesangial NO synthesis and release.