Altered Regulation of Renal Nitric Oxide and Atrial Natriuretic Peptide Systems in Lipopolysaccharide-induced Kidney Injury.
10.4196/kjpp.2011.15.5.273
- Author:
Eun Hui BAE
1
;
In Jin KIM
;
Seong Kwon MA
;
Jong Un LEE
;
Soo Wan KIM
Author Information
1. Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757, Korea. skimw@chonnam.ac.kr
- Publication Type:Original Article
- Keywords:
Lipopolysaccharide;
Atrial natriuretic peptide;
Nitric oxide;
Guanylyl cyclase
- MeSH:
Animals;
Atrial Natriuretic Factor;
Creatinine;
Guanosine Monophosphate;
Guanylate Cyclase;
Humans;
Immunoblotting;
Kidney;
Male;
Neprilysin;
Neurons;
Nitric Oxide;
Nitric Oxide Synthase;
Nitric Oxide Synthase Type II;
Nitroprusside;
Plasma;
Rats;
Real-Time Polymerase Chain Reaction;
Receptors, Peptide;
Relaxation;
RNA, Messenger;
Sepsis;
Sodium;
Veins
- From:The Korean Journal of Physiology and Pharmacology
2011;15(5):273-277
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
