Gentamicin treatment increases mesangial cell nitric oxide production.

Gentamicin-induced decreases in glomerular filtration rate have been associated with a marked decline in the glomerular capillary ultrafiltration coefficient which could be mediated by mesangial cell contraction. We have assessed a possible role of endogenous nitric oxide (NO) as a modulator of the proliferative and contractile effects of gentamicin on mesangial cells. NO synthesis and release, measured as nitrite production, 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 mesangial cells; cell treatment with gentamicin plus L-arginine significantly decreased the contractile effect of gentamicin. Gentamicin increased both [3H]thymidine incorporation into DNA and viable cell number; when L-arginine was added together with gentamicin, this abolished the effect of gentamicin on mesangial cell proliferation. The present studies demonstrate that gentamicin induces the expression of mac-iNOS and produces contraction and proliferation in mesangial cells. These actions seem to be modulated by mesangial NO synthesis and release.