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CORRECTION OF MORPHOFUNCTIONAL DISTURBANCES ARISING WHEN MODELLING PREECLAMPSIA WITH RESVERATROL AND NICORANDIL

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.

Иллюстрации

 

Figure 1A. Histological picture of the kidney in the modelling of ADMA-like preeclampsia. Note: (A ) – the glomerule of an intact animal. ( B ) the glomerule of an animal with ADMA-like preeclampsia. ×200.

Figure 1B. Histological picture of the kidney in the modelling of ADMA-like preeclampsia. Note: (A ) – the glomerule of an intact animal. ( B ) the glomerule of an animal with ADMA-like preeclampsia. ×200.

 

Figure 2A. Histological picture of the placenta in the modelling of ADMA-like preeclampsia. Note: (A ) type of intact placenta. ( B ) ADMA-like preeclampsia. Vacuolar degeneration of giant cell trophoblast; dystrophic changes in the decidual layer, foci of necrosis at the border of the giant cell trophoblast and decidual tissue. ×200.

Figure 2B. Histological picture of the placenta in the modelling of ADMA-like preeclampsia. Note: (A ) type of intact placenta. ( B ) ADMA-like preeclampsia. Vacuolar degeneration of giant cell trophoblast; dystrophic changes in the decidual layer, foci of necrosis at the border of the giant cell trophoblast and decidual tissue. ×200.

Figure 3A. Morphological picture of kidneys and placenta in animals with correction of ADMA-like preeclampsia by resveratrol. Note : ( A ) kidney; ( B ) placenta. ×200.

Figure 3B. Morphological picture of kidneys and placenta in animals with correction of ADMA-like preeclampsia by resveratrol. Note : ( A ) kidney; ( B ) placenta. ×200.

Figure 4A. Effect of resveratrol and nicorandil in combination with amlodipine on microcirculation in the placenta with ADMA-like preeclampsia.

Notes : * - р<0.05 in comparison with the group of intact animals; y - р<0.05 in comparison with the L-NAME group.

Figure 4B. Effect of resveratrol and nicorandil in combination with amlodipine on  plasma NO x content with ADMA-like preeclampsia.

Notes : * - р<0.05 in comparison with the group of intact animals; y - р<0.05 in comparison with the L-NAME group.

Figure 4C. Effect of resveratrol and nicorandil in combination with amlodipine on  proteinuria with ADMA-like preeclampsia.

Notes : * - р<0.05 in comparison with the group of intact animals; y - р<0.05 in comparison with the L-NAME group.

Figure 4D. Effect of resveratrol and nicorandil in combination with amlodipine on  swelling of the large omentum with ADMA-like preeclampsia.

Notes : * - р<0.05 in comparison with the group of intact animals; y - р<0.05 in comparison with the L-NAME group.

Figure 5A. Morphological picture of kidneys and placenta in animals with correction of ADMA-like preeclampsia by nicorandil in combination with amlodipine. Note : ( A ) kidney; ( B ) placenta. ×200.

Figure 5B. Morphological picture of kidneys and placenta in animals with correction of ADMA-like preeclampsia by nicorandil in combination with amlodipine. Note : ( A ) kidney; ( B ) placenta. ×200.

Figure 6A. Effect of resveratrol and nicorandil in combination with glibenclamide on microcirculation in the placenta with ADMA-like preeclampsia.

Notes : * - р<0.05 in comparison with the group of intact animals; y - р<0.05 in comparison with L-NAME group.

Figure 6B. Effect of resveratrol and nicorandil in combination with glibenclamide on plasma NO x concentration with ADMA-like preeclampsia.

Notes : * - р<0.05 in comparison with the group of intact animals; y - р<0.05 in comparison with L-NAME group.

Figure 6C. Effect of resveratrol and nicorandil in combination with glibenclamide on  proteinuria with ADMA-like preeclampsia.

Notes : * - р<0.05 in comparison with the group of intact animals; y - р<0.05 in comparison with L-NAME group.

Figure 6D. Effect of resveratrol and nicorandil in combination with glibenclamide on swelling of the large omentum with ADMA-like preeclampsia.

Notes : * - р<0.05 in comparison with the group of intact animals; y - р<0.05 in comparison with L-NAME group.

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