Nitric oxide synthase and VEGF expression in full-term placentas of obese women.

An adequate placental vascularization allows the proper development of the fetus and it is crucial for the gestational success. A number of factors regulate angiogenesis, including vascular endothelial growth factor (VEGF), which induces the synthesis of nitric oxide (NO), a potent vasodilator produced by three different nitric oxide synthase (NOS) isoforms. NO is essential to maintain a low vascular resistance in the fetoplacental circulation, although at high concentrations, it may combine with excess superoxide to produce peroxynitrite, which reacts with proteins giving rise to nitrotyrosine. Since obesity, whose incidence is increasing worldwide, is characterized by a low-grade inflammatory state and increased levels of oxidative and nitrative stress, both affecting placental function, our aim was to evaluate the expression of VEGF, eNOS, and iNOS in full-term placentas obtained from normal weight and pre-pregnancy obese women by means of immunohistochemistry and real-time PCR. Moreover, we assessed the NO levels and the nitrotyrosine immunoexpression in the same sample groups. Our results show a significantly higher immunohistochemical expression of VEGF and eNOS in the endothelium of placentas from obese women than in controls, whereas the immunoexpression of iNOS was comparable in the two groups. These data agree with those of the gene expression analysis, thus suggesting the possible existence of a compensatory mechanism for changes in placental blood flow associated with obesity. As concerns nitrotyrosine and NO levels, we observed a significant increase in placental tissue from obese women which may contribute to the development of metabolic and cardiovascular diseases both in the mother and the offspring.

Anorexia nervosa: a role for L-arginine supplementation in cardiovascular risk factors?

OBJECTIVE: The aim of the present study was to evaluate the effects of a short-term oral L-arginine treatment on platelet NO production, intracellular calcium concentration, iNOS and eNOS expression, in AN patients. METHOD: Forty outpatients belonging to restricting subtype and 40 normal participants age and sex matched were enrolled in the study. RESULTS: NO production was significantly elevated in the platelets from AN patients compared with controls while [Ca(2+)](i) was significantly decreased in patients with respect to controls. Western blot analysis demonstrated that iNOS isoform was more pronounced in the cell lysates from AN patients than controls. After supplementation with L-arginine, both NO production and [Ca(2+)](i) seem to return to control levels, suggesting a probable recovery of their metabolisms. The same was found after western blot analysis of NOS expression. DISCUSSION: The results here proposed can be considered highly indicative of a positive effect of L-arginine supplementation on platelet NO production in AN patients.

Lipoproteins obtained from anorexia nervosa patients induce higher oxidative stress in U373MG astrocytes through nitric oxide production.

Eating disorders (ED) are a group of important psychiatric disorders that affect young men and women, and can have serious consequences. Among all ED, anorexia nervosa (AN) is the most typical but also the most severe. The pathogenesis of AN is multifactorial and a great variety of cognitive deficits may contribute to its pathogenesis. The present study is aimed to measure NO and peroxynitrite production, iNOS and nNOS expression by Western immunoblot after incubation of AN lipoproteins at different times with human astrocytoma cells. The AN-HDL treated cells showed an increased production of NO at 3 h versus control-HDL treated cells and a decreased production at 24 h. Regarding LDL, a significant increase of NO production was obtained both at 3 and 24 h. The AN-HDL and AN-LDL treated cells showed an increased production of peroxynitrite both at 3 and 24 h compared to control lipoproteins. Densitometric analysis of bands indicated that both iNOS and nNOS protein levels were significantly higher in the cells incubated with AN lipoproteins compared to cells incubated with control lipoproteins both at 3 and 24 h. Although the pathogenesis of AN remains uncertain, evidence exists that modifications to the lipoprotein profile and cholesterol, structural alterations of phospholipids and integral constituents of myelin and synaptosomes may be related to psychotic disorders and body image distortion common to AN. Thus, a relevant pathophysiological association between NO and depression is certainly a possibility, as well as a central role played by NO in the pathogenesis.