The online version of this article (doi:10.1186/1758-5996-6-17) contains supplementary material, which is available to authorized users.
The author’s declare that they have no competing interests.
BSD reviewed the subject, searched for studies in databases, selected articles to include in the review and wrote the manuscript. CBL participated in the search and selection of articles and helped to draft the manuscript. RF helped in selection and helped to draft the manuscript. LHC conceived of the study, participated in coordination and helped to draft the manuscript. All authors read and approved the final manuscript.
About 30% of patients with type 2 diabetes mellitus develop clinically overt nephropathy. Hyperglycemia is necessary, but not sufficient, to cause the renal damage that leads to kidney failure. Diabetic nephropathy (DN) is a multifactorial disorder that results from interaction between environmental and genetic factors. In the present article we will review the role of the nitric oxide synthase (NOS) in the pathogenesis of DN.
Nitric oxide (NO) is a short-lived gaseous lipophilic molecule produced in almost all tissues, and it has three distinct genes that encode three NOS isoforms: neuronal (nNOS), inducible (iNOS) and endothelial (eNOS).
The correct function of the endothelium depends on NO, participating in hemostasis control, vascular tone regulation, proliferation of vascular smooth muscle cells and blood pressure homeostasis, among other features. In the kidney, NO plays many different roles, including control of renal and glomerular hemodynamics. The net effect of NO in the kidney is to promote natriuresis and diuresis, along with renal adaptation to dietary salt intake.
The eNOS gene has been considered a potential candidate gene for DN susceptibility. Three polymorphisms have been extensively researched: G894T missense mutation (rs1799983), a 27-bp repeat in intron 4, and the T786C single nucleotide polymorphism (SNP) in the promoter (rs2070744). However, the potential link between eNOS gene variants and the induction and progression of DN yielded contradictory results in the literature.
In conclusion, NOS seems to be involve in the development and progression of DN. Despite the discrepant results of many studies, the eNOS gene is also a good candidate gene for DN.
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- Nitric oxide system and diabetic nephropathy
Bruno Schmidt Dellamea
Cristiane Bauermann Leitão
Luis Henrique Canani
- BioMed Central
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