Behavioral, electrophysiological and neuropathological characteristics of the occurrence of hypertension in pregnant rats

Leandro F Oliveira,Jean Faber,Erika E Nishi,Esper A Cavalheiro,Daniel J L L Pinheiro,Selvin Z Reyes-Garcia,Milene S Ormanji,Laís D Rodrigues

doi:10.1038/s41598-019-40969-w

Abstract

Pre-eclampsia (PE) affects approximately 2 to 8% of pregnant women, causing blood pressure above 140 × 90 mmHg and proteinuria, normally after the 20th gestation week. If unsuccessfully treated, PE can lead to self-limited seizures (Eclampsia) that could eventually result in death of the mother and her fetus. The present study reports an experimental model of preeclampsia hypertension in pregnant (HP) and non-pregnant (H) Wistar rats by partially clamping one of their renal arteries. Pregnant (P) and non-pregnant (C) controls were provided. Differently from controls (C and P), H and HP animals presented a steady rise in BP two weeks after renal artery clamping. Injection of pentylenetetrazol (PTZ) induced behavioral and electroencephalographic seizures in all groups, which were increased in number, duration, amplitude and power accompanied by decreased latency in HP animals (p < 0.05). Consistent results were obtained in in vitro experimentation. Immunohistochemistry of hippocampus tissue in HP animals showed decreased density of neurons nuclei in CA1, CA3 and Hilus and increased density of astrocytes in CA1, CA3 and gyrus (p < 0.05). The present findings show that the clamping of one renal arteries to 0.15 mm and PTZ administration were able to induce signs similar to human PE in pregnant Wistar rats.

Highlights

The increase in blood pressure during pregnancy, without known etiology characterizes gestational hypertensive syndrome (GHS)[1]
systolic blood pressure (SBP) on days 14 and 19, was significantly higher in animals submitted to clamping of the left renal artery (H and hypertension in pregnant (HP) groups) when compared to those of the groups C and P (H = 27.63; p < 0.0001 and H = 30.12; p < 0.0001, respectively)
On day 19, groups H and HP differed from groups C and P (F = 23.02; p < 0.0001) by displaying levels characteristic of proteinuria in human preeclampsia albumin levels in H and HP showed no statistically significant difference (Fig. 2A)

Summary

Introduction

The increase in blood pressure during pregnancy, without known etiology characterizes gestational hypertensive syndrome (GHS)[1]. Preeclampsia (PE), a pathologic condition frequently occurring in late pregnancy characterized by edema, proteinuria and hypertension, is one of the hypertensive conditions classified as gestational hypertension syndromes[1]. It affects about 2 to 8% of pregnant women[2] and epidemiological studies showed that approximately 76,000 pregnant women and 500,000 fetuses die due to PE annually[2]. The risk of preeclampsia involves its progression to eclampsia, a self-limited seizure condition that can lead to coma and death of the pregnant woman and her fetus[12,13,14]. Medical management of PE is fundamentally directed towards the critical conditions with emphasis on blood pressure control and seizure suppression[15], which leaves a narrow margin, if any, to try alternative methods or www.nature.com/scientificreports/

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Conclusion