Gentamicin decreases guanylyl cyclase activity in rat glomerulus.
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.
Bae
Eun Hui
EH
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
Oh
Yoon Wha
YW
Park
Jeong Woo
JW
Ma
Seong Kwon
SK
Choi
Ki Chul
KC
Lee
Jongun
J
Kim
Suhn Hee
SH
Kim
Soo Wan
SW
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
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