Correction of morphofunctional disturbances arising when modelling Preeclampsia with resveratrol and nicorandil

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DOI:

https://doi.org/10.3897/rrpharmacology.4.25528

Abstract

Introduction: Preeclampsia is one of the most serious diseases of the second half of pregnancy and is surely amongst the top three causes of maternal mortality. Therefore, the creation of new drugs for preventing and correcting preeclampsia is an urgent task.

Methods: In the experiment, an ADMA-like L-NAME-induced model of preeclampsia was reproduced. To assess the emerging morphofunctional disorders, the following parameters were used: blood pressure, endothelial dysfunction coefficient, microcirculation in the placenta, proteinuria, fluid content in the large omentum, concentration of terminal metabolites in the blood plasma, morphological state of the placenta and kidneys and morphometric parameters of the foetus.

Results and Discussion: Injection of L-NAME into the animals from the 14th to the 20th day of pregnancy causes disorders: an increase in systolic and diastolic blood pressure by 1.4 and 1.5 times, an increase in proteinuria by 3.3 times and an increase in the fluid content in a large omentum from 45.82 ± 1.82% to 54.73 ± 1.96%, which correspond to disorders due to preeclampsia in pregnant women. There was also a disturbance of endothelial function, as evidenced by an increase in the coefficient of endothelial dysfunction (CED) by 2.9 times. The use of resveratrol leads to a pronounced correction in the changes that occur: a decrease in systolic and diastolic arterial pressure by 1.2 and 1.3 times, a decrease in proteinuria by a factor of 1.9 and a decrease in the fluid content in the large omentum to 50.00 ± 1.25%. The use of nicorandil leads to a pronounced correction in the resulting changes: a decrease in the diastolic blood pressure by 1.14 times, a decrease in proteinuria by a factor of 1.7 and a decrease in the fluid content in the large omentum to 50.57 ± 2.08%. CED decreased 1.7 times. When combining their use with amlodipine, the positive effects increased: systolic and diastolic blood pressure decreased 1.13 and 1.24 times and 1.14 and 1.23 times, respectively, proteinuria decreased 2.7 and 2.3 times, the fluid content in the large omentum was reduced to 44.54 ± 1.80% and 46.73 ± 1.30%. CED decreased 1.7 and 2.3 times. The administration of glibenclamide together with resveratrol and nicorandil removes a significant part of their positive effects.

Conclusion: Resveratrol and nicorandil have a significant positive effect in the correction of morphofunctional disorders in animals with ADMA-like preeclampsia. Activation of K+ATP channels plays a significant role in the realisation of their positive effects.

Keywords:

resveratrol, nicorandil, preeclampsia, pharmacological preconditioning, K ATP channels, rats, ADMA

Author Contribution

Elena G. Stupakova, Kursk State Medical University

Assistant to the Department of Obstetrics and Gynaecology, Faculty of Postgraduate Education. The author had a leading role in planning and performing the experiment, analysing the data and literature and writing the article.

Galina A. Lazareva, Kursk State Medical University

Doctor of Medical Sciences, Professor, Head of the Department of Obstetrics and Gynaecology, Faculty of Postgraduate Education. The author took part in planning experiments, analysed the literature and participated in interpreting the data.

Vladimir V. Gureev, Kursk State Medical University

Doctor of Medical Sciences, Associate Professor of the Department of Pharmacology and Clinical Pharmacology. The author participated in planning the experiments, analysed the literature and participated in interpreting the data. 

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Published

28-03-2018

How to Cite

Stupakova EG, Lazareva GA, Gureev VV (2018) Correction of morphofunctional disturbances arising when modelling Preeclampsia with resveratrol and nicorandil. Research Results in Pharmacology 4(1): 59–71. https://doi.org/10.3897/rrpharmacology.4.25528

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Review article

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