L-NAME-induced Preeclampsia: correction of functional disorders of the hemostasis system with Resveratrol and Nicorandil

Abstract

Introduction. Preeclampsia is a formidable disease of the second half of pregnancy, leading to severe complications, including disability and even death. Many authors have recognized the correlation between the severity of preeclampsia and the degree of disturbances in the hemostasis system. In this regard, the objective of this study was to assess inhibition of platelet aggregation and the possibility of its correction with resverаtrol and nicorandil. Materials and methods. The study was performed on 250 mature white Wistar female rats weighing 250–300 g. The platelet aggregation induced by ADP, collagen, ristomycin, adrenaline was determined, as well as PTT, TT, aPTT, fibrinogen, and the clotting time. Results and discussion. Introduction of resverаtrol and nicorandil resulted in a decrease in thrombocyte aggregation capacity from 53.8 ± 2.60% to 22.1 ± 1.25% and 37.1 ± 1.79%, respectively, when using ADP as an inducer. The clotting time was from 841 ± 42 s up to 1135 ± 33 s and 1034 ± 26 s, respectively. In addition, there was an increase in temporal parameters of plasma-coagulation hemostasis and a decrease in plasma fibrinogen content. The use of glibenclamide resulted in partial cancellation of the positive effects of resverаtrol and nicorandil, with an increase in platelet aggregation to 28.9 ± 1.8% and 43.9 ± 1.2% when using ADP as an inducer and a decrease in the thrombosis time to 988 ± 26 s and 950 ± 22 s, respectively. Conclusion. In animals with experimental preeclampsia, there were disturbances in the hemostasis system, comparable to those in the clinical situation. The use of resverаtrol and nicorandil leads to a pronounced correction of hemostasis parameters. The positive effects of the studied pharmacological agents are mediated by several mechanisms, including K+ATP channels.

Cross-Talk between Oxidative Stress and Inflammation in Preeclampsia

“…Finally, despite the relationship mentioned between AGEs, inflammation, and oxidative stress in PE, there are few studies that used antioxidant and anti-inflammatory compounds in an associated way to prevent/minimize the adverse consequences to mother and fetus health. Stupakova et al [88], in turn, aimed to evaluate the inhibition of platelet aggregation and the possibility of correction with resveratrol and nicorandil, in a rat model with PE induced by L-NAME. The findings were positive in relation to the drugs tested in order to aid in the homeostasis of the affected animals.…”

Correction of morphofunctional disorders of the cardiovascular system with asialized erythropoietin and arginase II selective inhibitors KUD 974 and KUD 259 in experimental preeclampsia

“…Estimation of the terminal NO metabolites. The level of NO metabolites (that is the total concentration of nitrates and nitrites, NOx) was determined by the colorimetric method, according to the staining pattern in the diazotization reaction of sulfonamide nitrite, which is a part of the reagent (Stupakova et al 2019).…”

“…The study was performed in 260 female Wistar rats, each weighing 250-300 g. ADMA-like preeclampsia was simulated by administration of a nonselective eNOS blocker N-nitro-L-arginine methyl ether (L-NAME) at a dose of 25 mg/kg/day intraperitoneally from the 14 th to 20 th day of pregnancy. One day after the last injection under anesthesia (chloral hydrate 300 mg/kg), hemodynamic parameters were recorded, and the endothelial function was studied using a sensor and a hardware complex for invasive measurement of hemodynamic parameters by Biopac (USA) and the AcqKnowledge 3.8.1 computer software (Stupakova et al 2019).…”

Pharmacological effects of the combined administration of a small dose of Acetylsalicylic acid and methyldopa in ADMA-like preeclampsia

“…Эндотелий является мощным эндокринным органом, участвующим в регуляции тонуса сосудов и поддержании их нормального строения, контроле реологических свойств крови и процессов местного воспаления. В норме антикоагулянтная и антитромботическая активность эндотелия преобладают над прокоагулянтными свойствами, однако в условиях повреждения данный баланс смещается в сторону прокоагуляции [5]. В настоящее время возрастает количество данных, свидетельствующих о том, что изменения ангиогенных факторов и коагулопатии ответственны за клинические проявления данного состояния.…”