Nitric oxide system and diabetic nephropathy

Abstract

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.

The Puerarin improves renal function in STZ-induced diabetic rats by attenuating eNOS expression

“…6,20 It is suggested that diabetes triggers dysfunction of NO bioavailability. Increased eNOS might be a compensatory mechanism to endothelial damage in type 2 diabetes by an excess production of ROS related to ineffective NO action.…”

“…5 The nitric oxide (NO) is believed to be involved in the early and late alterations of glomerular hemodynamics due to diabetes. [6][7][8] There are at least three NO-synthases, named neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS) that are present within the kidney. 9 Several studies have demonstrated that increased eNOS expression seems to be involved in the development and progression of DN.…”

Achalasia Is Associated With eNOS4a4a, iNOS22GA, and nNOS29TT Genotypes: A Case-control Study

“…11,12 The genes encoding for these isoforms are located in the human chromosomes 7q36, 17q11.2-q12, and, 12q24.2, respectively, which have several polymorphisms. 11,[13][14][15][16][17][18][19] Polymorphisms in eNOS, iNOS, and nNOS genes result in occurrence of either "high" or "low" producer alleles. Subjects homozygous for the high-producer alleles synthesize the highest amount of NO, those homozygous for the low-producer alleles the least, while heterozygotes produce an intermediate amount.…”

Pharmacoeconomical Approval of Genotyping Eligibility in Patients With Diabetes Mellitus Type 2 Taking Metformin

“…Тем не менее в некоторых исследованиях была выявлена ассоциация генотипа гомозиготы по аллели Т с инсулинорезистентностью у пациентов с СД2 типа и кар-диомиопатиями среди европейцев [6] и японцев [7], а также с повышенным уровнем глюкозы в крови у жителей Саудовской Аравии [8]. Роль уровня NO, в частности, имеет большое значение в вероятности наступления таких осложнений СД2, как нефропатия [9,10], ретинопа-тия [11], кардиомиопатия [12].…”