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.
Rivas-Cabañero
L
L
Instituto Reina Sofia de Investigacion, Nefrologica Departamento de Fisiologia y Farmacologia, Universidad de Salamanca, Spain.
Rodríguez-López
A M
AM
Martínez-Salgado
C
C
Saura
M
M
Lamas
S
S
López-Novoa
J M
JM
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D005839:Gentamicins / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000166:cytology* / Q000201:enzymology; D007150:Immunohistochemistry; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D009573:Nitrites; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase