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. Conclusion: GM-induced nephropathy may be causally related with decreased guanylyl cyclase activities in the glomerulus.

ACE2 activator diminazene aceturate exerts renoprotective effects in gentamicin-induced acute renal injury in rats

“…Interestingly, treatment with DIZE attenuated the increased urine osmolality in animals with GM-induced nephropathy. As we also observed in the present study, this increase in urine osmolality, which is described as a characteristic feature of ATN caused by GM administration, is not accompanied by changes in plasma osmolality (43,44). These findings corroborate previous data regarding Ang-(1-7) administration in rats, signalizing to an ACE2-mediated enhancement of the alternative RAS axis, in accordance to our results (45).…”