L-arginine-nitric oxide pathway and oxidative stress in plasma and platelets of patients with pre-eclampsia

Abstract

Pre-eclampsia (PE), a syndrome of pregnancy-induced hypertension, continues to be a leading cause of maternal and fetal morbidity and mortality. The aim of this study was to investigate whether changes in oxidative status are correlated with alterations in the L-arginine-nitric oxide pathway and platelet aggregation in PE. Plasma and platelets from women with PE (n=24) or normotensive pregnancy (NP, n=27) recruited in the third trimester of gestation were used to measure oxidative damage assessed by protein carbonyl content, antioxidant activities of superoxide dismutase (SOD), catalase (CAT) and nitrite levels. Transport of L-[(3)H]-arginine, as well as the activities of the nitric oxide (NO) synthase (eNOS and inducible NO synthase (iNOS)) and platelet aggregation, were also evaluated. Plasma nitrite levels and the activities of SOD and CAT were reduced in PE (5.2±2.7, 3.4±0.8, 0.3±0.4, respectively, P<0.05) compared with NP (8.7±2.3, 6.7±3.1, 1.0±0.5, respectively), whereas protein carbonyl content and L-arginine levels were not significantly different between PE and NP groups. In platelets, L-arginine transport was reduced in PE (19.2±10.5, P<0.05) compared with NP (62.0±31.1), whereas the NOS activity, eNOS and iNOS expression, nitrite levels and platelet aggregation were unaffected. Protein carbonyl content was increased, and CAT activity was reduced in platelets from PE (0.03±0.02, 0.55±0.30, respectively, P<0.05), compared with NP (0.005±0.005, 1.01±0.36, respectively). The data suggest that a systemic impairment of antioxidant defense mechanisms is associated with decreased plasma nitrite levels, which may contribute to hypertension in PE. Oxidative stress may contribute to the reduced influx of L-arginine in platelets. Compensatory mechanisms may contribute to the maintenance of NO production and its modulatory role on platelet function.

Inhibition of the JAK2/STAT3/SOSC1 Signaling Pathway Improves Secretion Function of Vascular Endothelial Cells in a Rat Model of Pregnancy-Induced Hypertension

“…NO plays an important role in regulating vasodilatation and vascular reactivity during pregnancy and its deficiency is associated with pathogenesis and maintenance of hypertension [21]. Pimentel et al found that the activity of SOD was reduced in the patients with preeclampsia [40], which indirectly confirms our finding. Intriguingly, the SOCS-JAK-STAT pathway plays an important role in vascular smooth muscle cell proliferation [30], which is closely associated with endothelial cytokines.…”

Decreased circulating anandamide levels in preeclampsia

“…Increasing evidence suggests that an exaggerated maternal systemic inflammatory response to pregnancy with an increase in the ratios of peripheral blood Th1/Th2 and Th17/ regulatory T cells, a systemic oxidative stress, as well as an imbalance between circulating angiogenic and anti-angiogenic factors plays a crucial role in the pathogenesis of the disease. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Endocannabinoids are endogenous ligands that bind to the similar receptor as delta-9-tetrahydrocannabinol (Δ 9 -THC), the most potent psychotropic constituent of marijuana. The most studied endocannabinoid is N-arachidonoylethanolamine (also known as anandamide), which is reported to have a central role in female reproduction, particularly in decidualization, 17 oviductal transport, 18 preimplantation embryo development, 19 timely embryo implantation and ensuring receptive uterine environment.…”

Bioactive factors in uteroplacental and systemic circulation link placental ischemia to generalized vascular dysfunction in hypertensive pregnancy and preeclampsia

“…During placental ischemia, oxidative stress reduces L-arginine in the platelets [138] while up-regulation of arginase enzyme may cause L-arginine to form urea instead of NO, thus decreasing NO in PE [139]. Also, hypoxia may induce an uncoupling reaction due to reduction in the NOS co-factor tetrahydrobiopterin (BH4) leading to ROS production and decreased NO formation [138].…”