Lipopolysaccharide administration significantly decreased creatinine clearance to 0.26 ml/min compared to 1.16 ml/min in controls, alongside enhanced NO/cGMP pathway and decreased ANP clearance.
Enhancement of the NO/cGMP pathway and a decrease in ANP clearance play a role in the pathogenesis of LPS-induced kidney injury in a rat model.
Absolute Event Rate: 0.26% vs 1.16%
p-value: p=<0.05
Nitric oxide (NO) and atrial natriuretic peptide (ANP) may induce vascular relaxation by increasing the production of cyclic guanosine monophosphate (cGMP), an important mediator of vascular tone during sepsis. This study aimed to determine whether regulation of NO and the ANP system is altered in lipopolysaccharide (LPS)-induced kidney injury. LPS (10 mg.kg(-1)) was injected in the tail veins of male Sprague-Dawley rats; 12 hours later, the kidneys were removed. Protein expression of NO synthase (NOS) and neutral endopeptidase (NEP) was determined by semiquantitative immunoblotting. As an index of synthesis of NO, its stable metabolites (nitrite/nitrate, NOx) were measured using colorimetric assays. mRNA expression of the ANP system was determined by real-time polymerase chain reaction. To determine the activity of guanylyl cyclase (GC), the amount of cGMP generated in response to sodium nitroprusside (SNP) and ANP was calculated. Creatinine clearance decreased and fractional excretion of sodium increased in LPS-treated rats compared with the controls. Inducible NOS protein expression increased in LPS-treated rats, while that of endothelial NOS, neuronal NOS, and NEP remained unchanged. Additionally, urinary and plasma NOx levels increased in LPS-treated rats. SNP-stimulated GC activity remained unchanged in the glomerulus and papilla in the LPS-treated rats. mRNA expression of natriuretic peptide receptor (NPR)-C decreased in LPS-treated rats, while that of ANP and NPR-A did not change. ANP-stimulated GC activity reduced in the glomerulus and papilla. In conclusion, enhancement of the NO/cGMP pathway and decrease in ANP clearance were found play a role in the pathogenesis of LPS-induced kidney injury.
Bae et al. (Sat,) conducted a other in Lipopolysaccharide-induced kidney injury (n=17). Lipopolysaccharide (LPS) vs. Control (saline) was evaluated on Creatinine clearance (ml/min) (p=<0.05). Lipopolysaccharide administration significantly decreased creatinine clearance to 0.26 ml/min compared to 1.16 ml/min in controls, alongside enhanced NO/cGMP pathway and decreased ANP clearance.