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: 7.63). 01/2005; 45(1):21-7. DOI: 10.1161/01.HYP.0000150158.42620.3e
Source: PubMed

ABSTRACT 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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    International Journal of Gynecology & Obstetrics 04/2006; 92(3):260-1. DOI:10.1016/j.ijgo.2005.12.015 · 1.56 Impact Factor
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    ABSTRACT: D IETS RICH IN FRUITS AND VEG-etables are among the rec-ommended lifestyle modifi-cations to lower blood pressure (BP) and to reduce cardiovas-cular disease risk, specifically in pre-hypertension or stage 1 hyperten-sion. 1,2 Although a variety of factors may contribute to the beneficial effects of plant foods, much attention has been given to the plant polyphenols. 3-5 Apart from fruits and vegetables, cocoa prod-ucts contribute to a major proportion of total phenol intake in Western coun-tries, 6,7 but they are not implemented in current dietary treatment advice. Co-coa liquor is especially rich in a spe-cific subclass of polyphenols, the fla-vanols, that have been suggested to mediate the favorable effects of cocoa products on cardiovascular health. 8 Consumption of flavanol-rich cocoa was found to lower BP and improve en-dothelial function in human interven-tion studies. However, these effects were observed with high doses of cocoa above the habitual intake (equivalent to at least 100 g of chocolate per day) and only in the setting of short-term in-terventions with a maximum fol-low-up of 2 weeks 9-12 or in single-dose assessments. 13,14 Hence, available clini-cal evidence is preliminary and insuf-ficient to recommend cocoa as an effi-cient antihypertensive dietary treatment option as summarized in a recent meta-analysis. 15 A particular concern is that the potential BP reduction contrib-Author Affiliations: Departments of Pharmacology (Drs Taubert, Roesen, and Schö mig) and Internal Medi-cine (Drs Lehmann and Context Regular intake of cocoa-containing foods is linked to lower cardiovascular mortality in observational studies. Short-term interventions of at most 2 weeks indi-cate that high doses of cocoa can improve endothelial function and reduce blood pres-sure (BP) due to the action of the cocoa polyphenols, but the clinical effect of low habitual cocoa intake on BP and the underlying BP-lowering mechanisms are unclear.