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.
Highlights
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
The endoteleoprotective properties of resveratrol and nicorandil (Danilenko 2013, Kochkarov 2009, Kochkarov et al 2006, Kochkarov 2008) were studied which could activate K+ATP channels (Tanaka et al 2010, Novaković et al 2015); we considered them to be the most promising for our studies
The degree of endothelial dysfunction in the experimental animals was assessed by the ratio of indices of endothelium-dependent vasodilation and endothelium-independent vasodilation with subsequent calculation of the coefficient of endothelial dysfunction (CED) (Korokin et al 2011, Pokrovsky et al 2006)
Summary
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. Preeclampsia has been one of the frequent and threatening complications of pregnancy and childbirth, leading to disability of mothers and their children (Gureev et al 2014, Kolgushkina 2000, Reznikova 2013, Shuvalov et al 2014, Savelyeva et al 2011, Federal State Statistics Service). The frequency of preeclampsia in pregnant women has increased in recent years and ranges from 7% to 20% (Kolgushkina 2000, Reznikova 2013, Shuvalov et al 2014, Federal State Statistics Service, Methodical letter 2016). There are several theories of preeclampsia development: the immunity theory, the theory of disadaptation, the theory of placental ischemia, the hormonal theory, the theory of toxic effects, the hereditary theory, etc. (Shuvalov et al 2014, Savelyeva et al 2011, Sidorova 2003)
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