Vascular endothelial dysfunction: a tug of war in diabetic nephropathy?
Vascular endothelium regulates vascular tone and maintains free flow of blood in vessels. Vascular endothelial dysfunction (VED) results in reduced activation of endothelial nitric oxide synthase (eNOS), reduced generation and bioavailability of nitric oxide (NO) and increased production of reactive oxygen species (ROS). The eNOS uncoupling in VED leads to eNOS mediated production of ROS that further damage the endothelial cells by upregulating the proinflammatory mediators and adhesion molecules. VED has been associated in the pathogenesis of hypertension, atherosclerosis, coronary artery diseases, diabetes mellitus and nephropathy. Diabetes is a chronic metabolic disorder characterized by hyperglycemia followed by micro and macrovascular complications. A correlation between diabetes and VED has been demonstrated in various studies. The downregulation of eNOS in diabetes has been noted to accelerate diabetic nephropathy. Moreover, various endogenous vasoconstrictors are also upregulated in diabetic nephropathy. VED has been shown to be involved in diabetic nephropathy by inducing nodular glomerulosclerosis followed by glomerular basement membrane thickness and mesangial expansion, which ultimately decline glomerular filtration rate (GFR). Thus it is suggested that diabetes-induced VED could be one of the culprits involved in the pathogenesis of diabetic nephropathy.
Balakumar
Pitchai
P
Cardiovascular Pharmacology Division, ISF College of Pharmacy, Moga 142 001, Punjab, India. pbala2006@gmail.com
Chakkarwar
Vishal Arvind
VA
Krishan
Pawan
P
Singh
Manjeet
M
D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000503:physiopathology*; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005786:Gene Expression Regulation; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III