title: S-nitrosoalbumin-mediated relaxation is enhanced by ascorbate and copper: effects in pregnancy and preeclampsia plasma.
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.
authors.affiliation: Magee-Womens Research Institute and Department of Environmental and Occupational Health, University of Pittsburgh, 204 Craft Ave, Pittsburgh, PA 15213, USA. rsireg@mwri.magee.edu
authors.forename: Robin E
authors.initials: RE
authors.lastname: Gandley
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Tyurin
authors.forename: Wan
authors.initials: W
authors.lastname: Huang
authors.forename: Antonio
authors.initials: A
authors.lastname: Arroyo
authors.forename: Ashi
authors.initials: A
authors.lastname: Daftary
authors.forename: Gail
authors.initials: G
authors.lastname: Harger
authors.forename: Jianfei
authors.initials: J
authors.lastname: Jiang
authors.forename: Bruce
authors.initials: B
authors.lastname: Pitt
authors.forename: Robert N
authors.initials: RN
authors.lastname: Taylor
authors.forename: Carl A
authors.initials: CA
authors.lastname: Hubel
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan
mesh_terms: D000328:Adult; D000818:Animals; D001205:Ascorbic Acid / Q000097:blood* / Q000494:pharmacology; D003300:Copper / Q000097:blood* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008638:Mesenteric Arteries / Q000187:drug effects; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D010069:Oxadiazoles / Q000494:pharmacology; D018384:Oxidative Stress; D010656:Phenylephrine / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000097:blood* / Q000503:physiopathology; D011247:Pregnancy; D011810:Quinoxalines / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D010069:Oxadiazoles; D011810:Quinoxalines; C091665:S-nitrosoalbumin; D010656:Phenylephrine; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; D003300:Copper; D001205:Ascorbic Acid; D019331:NG-Nitroarginine Methyl Ester