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(Hypertension. 2005;45:21.)
© 2005 American Heart Association, Inc.

Scientific Contributions

S-Nitrosoalbumin–Mediated Relaxation Is Enhanced by Ascorbate and Copper

Effects in Pregnancy and Preeclampsia Plasma

Robin E. Gandley; Vladimir A. Tyurin; Wan Huang; Antonio Arroyo; Ashi Daftary; Gail Harger; Jianfei Jiang; Bruce Pitt; Robert N. Taylor; Carl A. Hubel; Valerian E. Kagan

From the Magee-Womens Research Institute and Departments of Environmental and Occupational Health (R.E.G., V.A.T., W.H., A.A., J.J., B.P., C.A.H., V.E.K.) and Obstetrics, Gynecology, and Reproductive Sciences (A.D., G.H., C.A.H.), Center for Free Radical and Antioxidant Health (R.E.G., V.A.T., J.J., B.P.), University of Pittsburgh, Pittsburgh, Pa; and the Department of Obstetrics, Gynecology and Reproductive Sciences (R.N.T.), University of California, San Francisco.

Correspondence to Robin E. Gandley, PhD, Magee-Womens Research Institute, 204 Craft Ave, Pittsburgh, PA 15213. E-mail rsireg{at}mwri.magee.edu

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 µmol/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.

Key Words: preeclampsia • pregnancy • nitric oxide • oxidative stress • antioxidants

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