Role of the Decreased Nitric Oxide Bioavailability in the Vascular Complications of Diabetes Mellitus

Abstract

This mini-review takes into consideration the physiology, synthesis and mechanisms of action of the nitric oxide (NO) and, subsequently, the causes and effects of the NO bioavailability impairment. In diabetes mellitus the reduced NO bioavailability is caused by the increased free radicals production, secondary to hyperglycemia. The reactive oxygen species oxidize the cofactors of the nitric oxide synthase, diminishing their active forms and consequently leading to a decreased NO production. Furthermore the decreased concentration of reduced glutathione results in a diminished production of nitrosoglutathione. These molecules are important intermediates of the NO pathway and physiologically activate the soluble guanylate cyclase. Their decrease in oxidative states of the cell, therefore, leads to a reduced cGMP production which represents the principal molecule that carries out NO's major effects. Finally we considered the eventual therapeutic strategies to improve NO bioavailability by acting on the causes of its decrease. Therefore the treatments proposed are based on the possibility to counteract the oxidation and, in this context, the physiopathological mechanisms strongly support the treatment with thiols.

Estimation of platelet distribution width in type 2 diabetic male subjects

“…ese platelet activation causes increase PDW in diabetic subjects and act as a risk factor for future cardiovascular disease. 21,22 In the present study, it may be concluded that increased platelet distribution width in type 2 diabetes mellitus. …”

Tumor Necrosis Factor/Sphingosine-1-Phosphate Signaling Augments Resistance Artery Myogenic Tone in Diabetes

“…Consequently, silent or asymptomatic microcirculatory dysfunction is now viewed as a key intervention point that can potentially alter the patient's clinical course. Many studies conclude that endothelial dysfunction, a broad range of abnormalities that disrupts the delicate balance between dilatory (most notably nitric oxide [35]) and constrictive mediators (36), is the mechanistic basis of enhanced microvascular contractility in diabetes (37,38). Our data do not support an endothelial basis for our model's phenotype: 1) endothelial-stimulated vasodilation is preserved, and 2) the PE dose-response relationship does not left shift, which would be expected if constitutive vasodilatory signals were attenuated.…”

Serum nitric oxide metabolites are associated with the risk of hypertriglyceridemic-waist phenotype in women: Tehran Lipid and Glucose Study

“…The mean (± SD) values and the proportions of baseline characteristics of the 3 participants with and without the HTW phenotype, in each sex, were compared using the 4 independent sample t test or Chi square test, respectively. 5 Dietary intakes of the study participants were compared across serum NOx tertiles using analysis 6 of covariance with adjustment for total energy intake. Serum TG levels and WC at baseline and 7 follow-up examinations were compared across serum NOx tertiles using analysis of variance and 8 Bonferroni pairwise comparison test.…”

“…A negative correlation between NOx concentration 4 and abdominal adiposity was also reported only in women in a cross-sectional investigation [21]. 5 To our knowledge, this controversial issue has not yet been investigated in the framework of a 6 prospective longitudinal examination; such a setting could probably help to better justify and 7 provide causality regarding the association between NOx and obesity. The main focus in this 8 study, therefore, was to assess whether serum NOx concentration, an indicator of systemic NO 9 synthesis, could predict the occurrence of hypertriglyceridemic-waist (HTW) phenotype, as a 10 dichotomous surrogate marker of visceral adiposity.…”