title: Gentamicin decreases guanylyl cyclase activity in rat glomerulus.
abstract: BACKGROUND
  Effects of gentamicin (GM) on the local natriuretic peptide (NP) and nitric oxide (NO) systems in the kidney were investigated.
  
  
  METHODS
  Male Sprague-Dawley rats (180-200 g) were intramuscularly injected with GM (100 mg/kg/day) for 5 days. The expression of NO synthase (NOS) isoforms was determined by Western blot analysis, and that of NPs by real-time polymerase chain reaction. The activity of guanylyl cyclase was also determined by the amount of guanosine 3',5'-cyclic monophosphate (cGMP) generated in responses to atrial natriuretic peptide (ANP) or sodium nitroprusside (SNP).
  
  
  RESULTS
  GM treatment resulted in renal failure in association with increases in urinary flow and the fractional excretion of sodium. Accordingly, the expression of inducible NOS was increased in the cortex, while that of endothelial NOS remained unchanged. The urinary excretion of NO metabolites was increased. The expression of ANP, brain natriuretic peptide and C-type natriuretic peptide mRNA was increased in the kidney. The cGMP production provoked by either ANP or SNP was decreased in the glomerulus, but not in the papilla.
  
  
  CONCLUSIONS
  GM-induced nephropathy may be causally related with decreased guanylyl cyclase activities in the glomerulus.
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Eun Hui
authors.initials: EH
authors.lastname: Bae
authors.forename: Yoon Wha
authors.initials: YW
authors.lastname: Oh
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Seong Kwon
authors.initials: SK
authors.lastname: Ma
authors.forename: Ki Chul
authors.initials: KC
authors.lastname: Choi
authors.forename: Jongun
authors.initials: J
authors.lastname: Lee
authors.forename: Suhn Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Soo Wan
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D005839:Gentamicins / Q000008:administration & dosage / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000502:physiology; D006162:Guanylate Cyclase / Q000378:metabolism*; D007273:Injections, Intramuscular; D007678:Kidney Glomerulus / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000235:genetics / Q000378:metabolism; D045265:Natriuretic Peptides / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D045265:Natriuretic Peptides; D012333:RNA, Messenger; D020098:Natriuretic Peptide, C-Type; D009569:Nitric Oxide; D012964:Sodium; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP