Role of copper in the relaxant action of <i>S</i>‐nitrosothiols in the rat anococcygeus muscle

Ng, Chi Wai; Najbar-Kaszkiel, Alicja T; Li, Chun Guang

doi:10.1046/j.1440-1681.2003.03845.x

Cited by 4 publications

(2 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, a Cu 1ϩ chelator (neocuproine) produces concentration-dependent inhibition of the relaxations from S-nitrosothiols (GSNO, SNAP) in the rat anococcygeus muscle, which indicates that Cu 1ϩ participates in the relaxant action of RSNO. 37 Likewise, depletion of Asc levels (as result of Cu/Albcatalyzed oxidation) has been shown to drastically decrease NO release from SNO-Alb and result in endothelial dysfunction. 38 It is possible that profound conformational changes of Alb on binding of fatty acids-particularly in the presence of Cu tightly bound to its N-terminal tripeptide Asp-Ala-His site 39 (located in a close proximity to S-nitrosylated Cys 34)-may lead to a decreased stability of its S-NO bond dissociation energy.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2005

View full text Add to dashboard Cite

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 mol/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 Ͼ90%, whereas no change in the SH-Alb (5%) response was observed. Preeclampsia plasma with higher levels of SNO-Alb caused arteries to relax 44.1Ϯ4.7%, whereas normal pregnancy plasma caused 11.9Ϯ4.2% relaxation (Pϭ0.007). 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 Ⅲ pregnancy Ⅲ nitric oxide Ⅲ oxidative stress Ⅲ antioxidants P reeclampsia is a major cause of maternal and neonatal morbidity and mortality. The clinical manifestations of this pregnancy-specific disorder include hypertension and proteinuria developing after 20 weeks of gestation. Placental abnormalities and maternal endothelial dysfunction/activation are thought to contribute to vasospasm and the onset of the maternal syndrome. It has been hypothesized that oxidative stress plays a role in the pathophysiology of preeclampsia. Evidence of oxidative stress in combination with profound depletion of plasma ascorbate (Asc) has been reported in women with preeclampsia. [1][2][3][4] Asc concentrations in women with preeclampsia are nearly half those of matched normal pregnant controls (Ϸ40 versus 25 mol/L). 5 The implications of this reduction in plasma Asc are currently not clear. Plasma Asc levels are inversely related to blood pressures in men without a history of hypertension. 6,7 Asc and vitamin E supplementation in women at high risk for preeclampsia was associated with a reduction in markers of endothelial dysfunction and in the incidence of preeclampsia. 5,8 Although the decreased incidence of preeclampsia was associated with decreased biochemical indices of oxidative stress and poor placental function, the me...

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2005

View full text Add to dashboard Cite

show abstract

“…It has been reported that some of these thionitrites have been detected in the submicromolar range in plasma and bronco-alveolar lavage fluid . Degradation of these RSNOs enzymatically − or nonenzymatically − is believed to release the NO to target tissues where it will play its assigned physiological role. Despite the ease with which the biologically relevant thiols can be nitrosated in aqueous solutions , there seems to be a general lack of kinetics data and mechanistic understanding of how the S -nitrosothiols are formed .…”

Section: Introductionmentioning

confidence: 99%

Formation and Stability of a Nitric Oxide Donor: S-Nitroso-N-acetylpenicillamine

Chipinda

Simoyi

2006

J. Phys. Chem. B

View full text Add to dashboard Cite

The formation, reaction dynamics, and detailed kinetics and mechanism of the reaction between nitrous acid and N-acetylpenicillamine (NAP) to produce S-nitroso-N-acetylpenicillamine (SNAP) was studied in acidic medium. The nitrous acid was prepared in situ by the rapid reaction between sodium nitrite and hydrochloric acid. The reaction is first order in nitrite and NAP. It is also first order in acid in pH conditions at or slightly higher than the pK(a) of nitrous acid. In lower pH conditions, the catalytic effect of acid quickly saturates. Higher acid concentrations also induce a faster decomposition rate of the SNAP, thus precluding the quantitative formation of SNAP from HNO2 and NAP. Both HPLC and quadrupole time-of-flight mass spectrometry techniques proved that SNAP was the sole product produced. No nitrosation occurred on the secondary amine center in NAP, and only the thiol group reacted to form the nitrosothiol. Cu(I) ions were found to be effective SNAP-decomposition catalysts. Cu(II) ions had no effect on the stability of SNAP. Ambient oxygen in reaction solutions was found to have no effect on initial rates of formation of SNAP, products obtained, and stability of SNAP. The formation of SNAP occurs through two distinct pathways. One involves the direct reaction of NAP and HNO2 to form SNAP and eliminate water, and the second pathway involved the initial formation of the nitrosyl cation, NO+, which then nitrosates the thiol. The bimolecular rate constant for the reaction of NAP and HNO2 was derived as 2.69 M(-1) s(-1), while that of direct nitrosation by the nitrosyl cation was 3.00 x 10(4) M(-1) s(-1). A simple reaction network made up of four reactions was found to be sufficient in simulating the formation kinetics and acid-induced decomposition of SNAP.

show abstract

References

2004

Nitrosation Reactions and the Chemistry of Nitric Oxide

View full text Add to dashboard Cite

Role of copper in the relaxant action of S‐nitrosothiols in the rat anococcygeus muscle

Cited by 4 publications

References 21 publications

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

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

Formation and Stability of a Nitric Oxide Donor: S-Nitroso-N-acetylpenicillamine

References

Contact Info

Product

Resources

About