S-nitrosoalbumin-mediated relaxation is enhanced by ascorbate and copper: Effects in pregnancy and preeclampsia plasma

Magee-Womens Research Institute and Department of Environmental and Occupational Health, University of Pittsburgh, 204 Craft Ave, Pittsburgh, PA 15213, USA.
Hypertension (Impact Factor: 6.48). 01/2005; 45(1):21-7. DOI: 10.1161/01.HYP.0000150158.42620.3e
Source: PubMed


S-nitrosoalbumin (SNO-Alb) is a major reservoir of releasable nitric oxide (NO) in plasma. In preeclampsia, a pregnancy-specific disorder associated with endothelial dysfunction, we previously found significant elevations in plasma SNO-Alb concentrations and decreased plasma ascorbate (Asc) levels. This increased SNO-Alb may result from low-plasma Asc if Asc, along with transition metals (eg, copper [Cu]) are necessary for release of NO from S-nitrosothiols. We propose that vasodilator effects of SNO-Alb, mediated by release of NO, are fully realized only when Asc/Cu availability is sufficient. Relaxation responses to SNO-Alb or the control reduced human serum albumin (SH-Alb), and responses to pooled plasma from normal or preeclamptic pregnancies were examined in isolated mouse arteries. Arteries preconstricted with phenylephrine were exposed to SNO-Alb or SH-Alb at physiologically relevant concentrations. When free Cu was added in excess (10 mumol/L), NO release was not dependent on Asc. However, when Cu was added at lower (physiological) levels, NO release was dependent on Asc. The addition of Asc and Cu to SNO-Alb stimulated vasodilatory responses in isolated arteries >90%, whereas no change in the SH-Alb (5%) response was observed. Preeclampsia plasma with higher levels of SNO-Alb caused arteries to relax 44.1+/-4.7%, whereas normal pregnancy plasma caused 11.9+/-4.2% relaxation (P=0.007). These data indicate that SNO-Alb alone or in plasma can act as a potent vasodilator, and that sufficient Asc/Cu promotes this action. We suggest that the higher circulating levels of SNO-Alb, in women with preeclampsia, reflect a deficiency in Asc/Cu-mediated release of NO from SNO-Alb.

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Available from: Jianfei Jiang, Jun 02, 2014
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    • "Vitamin C, vitamin A, vitamin E, beta carotene, glutathione levels, and iron-binding capacity are lower in the maternal circulation of women with preeclampsia than women with a normal pregnancy. Gandley et al (2005) suggested that the higher circulating levels of S-nitrosoalbumin in women with preeclampsia reflect a deficiency in ascorbatemediated release of NO from S-nitrosoalbumin. These deficiencies in antioxidants may have important vascular effects in preeclampsia. "

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    • "Furthermore, this report shows that nitrosoproteins breakdown in PE restores NO levels to those in NP. As suggested by others [3], impaired decomposition of S-nitrosoprotein during PE might explain, at least partially, the abnormal intracellular action of NO [4] "

    International Journal of Gynecology & Obstetrics 04/2006; 92(3):260-1. DOI:10.1016/j.ijgo.2005.12.015 · 1.54 Impact Factor
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    • "S-nitrosoproteins have been detected in many cell types including the endothelium [14]. The presence of increasing concentrations of reducing agents such as vitamin C and cysteine leads to the rapid release of NO and progressive decrease in detectable S-nitrosoproteins [14], [19], [25]. This process is enhanced by the presence of biologically relevant reduced transition metals such as copper and iron [24], [25]. "
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    ABSTRACT: Free nitric oxide (NO) reacts with sulphydryl residues to form S-nitrosothiols, which act as NO reservoirs. We sought to determine whether thiol-preserving agents and antioxidants, such as dithiothreitol (DTT) and vitamin C, induce NO release from S-nitrosylated proteins in endothelial cell cultures to promote angiogenesis. NO release was measured directly in cell supernatants using a Sievers NO Analyser, and in vitro angiogenesis was assessed by quantifying capillary-like tube network formation of porcine aortic endothelial cells (PAEC) on growth factor-reduced Matrigel. Incubation of PAEC with DTT or vitamin C significantly increased NO release in a concentration-dependent manner. However, the nitric oxide synthase (NOS) inhibitors, L-NNA and L-NIO, had no effect on DTT- or vitamin C-induced NO release, and there was no concomitant increase in the phosphorylation of endothelial NOS at serine-1177 following DTT or vitamin C treatment. DTT and vitamin C increased capillary-like tube network formation by nine- and two-fold, respectively, and the addition of copper ions doubled the effect of vitamin C. Surprisingly, DTT maintained endothelial tube networks for up to one month under serum-free conditions, and selective inhibitors of guanylyl cyclase (ODQ) and PKG (KT-5823) blocked this, demonstrating the requirement of cyclic GMP and PKG in this process. Both DTT and vitamin C are capable of releasing sufficient NO from S-nitrosothiols to induce capillary morphogenesis. This study provides the first evidence that increased denitrosylation leads to increased bioavailability of NO, independent of NOS activity, to promote sustained angiogenesis.
    PLoS ONE 02/2006; 1(1):e25. DOI:10.1371/journal.pone.0000025 · 3.23 Impact Factor
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