Endothelial nitric oxide in diabetes mellitus: too much or not enough?
Vascular complications are the leading cause of increased mortality in patients with diabetes mellitus. Endothelial dysfunction, characterised by impaired endothelium-dependent vasoreactivity, is the first sign of blood vessel damage that precedes morphological changes of the vessel wall. With other factors altered bioavailability of nitric oxide, the most potent endothelium-derived vasodilator, contributes to the changes in vascular tone and integrity. In addition to the impairment of vascular reactivity and permeability, other anti-atherosclerotic functions of nitric oxide are also diminished, which may result in activated monocyte, leukocyte and platelet adhesion to the endothelium, increased platelet aggregation, lipoprotein influx to the subendothelial space and smooth muscle proliferation. Hyperglycaemia-induced increased oxidative stress and impairment of antioxidant defence are suggested to play a role in the pathomechanism of vascular damage, partly by influencing nitric oxide. Both in experimental and clinical Type 1 and Type 2 diabetes mellitus the apparently conflicting data of increased, unaltered or diminished nitric oxide action suggests a complex, time and localisation-dependent alteration of vascular function. The understanding of the mechanisms that lead to diabetic endothelial dysfunction and its early detection are necessary to establish appropriate intervention to prevent irreversible atherosclerotic vessel damage in patients with diabetes mellitus.
Farkas
K
K
3rd Medical Department, Bajcsy-Zsilinszky Hospital, Budapest, Hungary. klaralex@mail.matav.hu
Sármán
B
B
Jermendy
G
G
Somogyi
A
A
D000818:Animals; D003920:Diabetes Mellitus / Q000201:enzymology* / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D009129:Muscle Tonus; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D014665:Vasodilator Agents
D014665:Vasodilator Agents; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III