Study of the effect of selective inhibitor of Arginase II KUD 975 and of low doses of Acetylsalicylic acid on the functional parameters of the cardiovascular system In experimental preeclampsia

Olga V Severinova,Vladimir V Gureev,Sofia S Lazareva,Galina A Lazareva,Lyudmila A Zhilinkova,Anastasia V Gureeva

doi:10.3897/rrpharmacology.5.47654

Olga V Severinova, Vladimir V Gureev + Show 4 more

Open Access

https://doi.org/10.3897/rrpharmacology.5.47654

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Abstract

Introduction: Over the past decade, preeclampsia has been the subject of an increased attention, as this complication is the most common cause of maternal mortality, triggering every third case of obstetric morbidity and taking lives of up to 50.000 young women worldwide each year. Despite a large number of ongoing studies, no clear algorithm for monitoring pregnant women with this pathology has been developed yet. Materials and methods: The study was conducted on 220 female Wistar rats weighing 250–300 g. In the experiment, ADMA-like preeclampsia model was used. Results and discussion: The introduction of L-NAME to the animals from the 14th till the 20th day of pregnancy causes the following disturbances: a rise in systolic and diastolic blood pressure in 1.4 and 1.5 times, an increase in proteinuria in 3.3 times and an increase in the content of fluid in the greater omentum from 44.39 ± 1.62% to 55.02 ± 1.74%, all of which correspond to the disorders in pregnant women in case of preeclampsia. The use of the selective inhibitor of arginase II KUD 975 (3mg/kg/day) in combination with acetylsalicylic acid (10mg/ kg/day) leads to a pronounced correction in the emerging changes: a decrease in systolic and diastolic blood pressure in 1.2 and 1.3 times, a decrease in proteinuria in 1.9 times and a decrease in the fluid content in the greater omentum. Conclusion: Selective inhibitor of arginase II KUD 975 and small doses of acetylsalicylic acid have a pronounced positive effect in the correction of morphofunctional disorders in animals with ADMA-like preeclampsia.

Highlights

Over the past decade, preeclampsia has been the subject of an increased attention, as this complication is the most common cause of maternal mortality, triggering every third case of obstetric morbidity and taking lives of up to 50.000 young women worldwide each year
The simulation of ADMA-like preeclampsia resulted in an increase in systolic and diastolic blood pressure from 127.6±1.5 mmHg and 91.9±5.63 mmHg up to 200.5±6.32 mmHg and 151±5.69 mmHg, respectively
There was a distortion of the ratio of endothelium-dependent and endothelium-independent vasorelaxations, which resulted in an increase in coefficient of endothelial dysfunction (CED) from 1.32±0.8% c.u. to 3.13±0.21 c.u

Summary

Introduction

Preeclampsia has been the subject of an increased attention, as this complication is the most common cause of maternal mortality, triggering every third case of obstetric morbidity and taking lives of up to 50.000 young women worldwide each year. Results and discussion: The introduction of L-NAME to the animals from the 14th till the 20th day of pregnancy causes the following disturbances: a rise in systolic and diastolic blood pressure in 1.4 and 1.5 times, an increase in proteinuria in 3.3 times and an increase in the content of fluid in the greater omentum from 44.39 ± 1.62% to 55.02 ± 1.74%, all of which correspond to the disorders in pregnant women in case of preeclampsia. Especially dangerous and attracting an increased attention are disturbances in the hemostatic system in preeclampsia (AlSheeha et al 2016, Severinova et al 2019)

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Conclusion