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.
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ABSTRACT: Interactie tussen AT1 en a1-adrenerge receptoren (Hoofdstuk 6) Carvedilol, de selectieve ß1-adrenoceptor antagonist metoprolol, de niet-selectieve ßadrenoceptor antagonist propranolol, en de a1-adrenoceptor antagonist prazosin beïnvloedden geen van allen de constrictoire respons van HCMA’s op Ang II. Ang II, na toevoeging aan het orgaan bad in een lage (non-constrictoire) concentratie, versterkte de respons op de a1-adrenoceptor agonist fenylefrine enorm. Zowel carvedilol als de AT1 receptor antagonist irbesartan remden deze door Ang II geïnduceerde potentiatie. Carvedilol remde eveneens de door Ang II versterkte ophoping van inositolfosfaten onder invloed van fenylefrine in hartspiercellen. Samenvattend kan gesteld worden dat AT1-a1-receptor ‘crosstalk’, mogelijk via inositolfosfaten, HCMA’s gevoeliger maakt voor a1-adrenoceptor agonisten. De a1-adrenoceptor blokkerende effecten van carvedilol zorgen er voor dat carvedilol dit potentiërende effect van Ang II tegen kan gaan. Dit verklaart waarom het bloeddrukverhogende effect van Ang II bij patiënten met hartfalen die behandeld worden met carvedilol kleiner is dan bij patiënten die behandeld worden met metoprolol.
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ABSTRACT: The purpose of this study was to evaluate the effects of Silymarin on vascular endothelial growth factor (VEGF), soluble VEGF Receptor-1 (sVEGFR-1) and Interleukin-1 alpha (IL-1α) levels in placental tissue samples of severely preeclamptic women. We conducted an in vitro study in Başkent University Faculty of Medicine, Ankara, Turkey between September 2008 and May 2009. A total of 16 placental tissue samples (8 from severe preeclamptic, and 8 from controls) were analysed. Placental samples were incubated, and VEGF, sVEGFR-1, and IL1-α were measured in culture media using an ELISA kit. The effect of Silymarin on these levels was investigated. Descriptive statistics were initially performed, followed by Mann Whitney U-test and Kruskal-Wallis test to compare means between groups. P values less than 0.05 were considered statistically significant. Eight patients were included in the severe preeclampsia (SP) group, whereas the remaining 8 patients were included in the control group. There were no significant correlations between gestational age and placental VEGF, sVEGFR-1 and IL-1α after 48 or 72 hours of incubation. Basal VEGF levels were lower in the SP group; however, it did not reach statistical significance. sVEGFR-1 and IL-1α levels were also similar between the SP and control groups (p>0.05). After 48 and 72 hours of incubation, sVEGFR-1 levels in Silymarin-added SP and control placental cultures were lower than in the samples without Silymarin addition; however, this difference also did not reach significance. Although we could not demonstrate a significant effect on placental cytokines, considering the role of vasospasm, inflammation, angiogenesis, endothelial cell activation, and oxidative stress in preeclampsia, the potential benefits of Silymarin should be evaluated in future trials with a larger sample size.03/2014; 15(1):30-35. DOI:10.5152/jtgga.2014.81592
Gastroenterology 01/2011; 140(5). DOI:10.1016/S0016-5085(11)61664-8 · 13.93 Impact Factor