Elsevier

Placenta

Volume 36, Issue 12, December 2015, Pages 1450-1454
Placenta

Effects of selective reduced uterine perfusion pressure in pregnant rats

https://doi.org/10.1016/j.placenta.2015.10.017Get rights and content

Highlights

  • Selective reduction of uterine pulse pressure (SRUPP) induces a hypertensive like state in pregnant rats.

  • SRUPP in pregnant rats is associated with an increase in oxidative stress.

  • In the SRUPP model the reduction in perfusion pressure is limited to the uterine arteries and utero-ovarian arteries.

  • SRUPP may become a useful tool in the study of pregnancy related hypertensive disease.

Abstract

Introduction

To assess the effects of selective reduced uterine perfusion pressure (SRUPP) in pregnant rats.

Methods

20 pregnant Sprague–Dawley rats were allocated either to an intervention group, exposed to SRUPP (n = 10) or a control group, exposed to sham surgery (n = 10). Such procedures were performed on gestational day (GD) 14. The Mean arterial pressure (MAP) was measured on GD14 (before surgery) and GD20. We measured 18 h proteinuria on GD20. On GD21, mean fetal (MFW) and placental (MPW) weights were obtained. Oxidative stress and angiogenic markers were measured in placental tissue and urine. Mann Whitney U or Independent samples T test were used when appropriate. A two-sided P < 0.05 indicated statistical significance.

Results

MAP on GD20 was higher in the intervention group (109 ± 1.7 mmHg) when compared with the control group (83 ± 1.5 mmHg) (P = 0.002). There was no significant difference in urinary protein excretion (117 ± 3.1 mg/24 h versus 136 mg ± 2.8/24 h, P = 0.18), MFW (4.14 ± 0.05 versus 4.39 ± 0.04 g, P = 0.19) or MPW (0.43 ± 0.008 versus 0.44 ± 0.006 g, P = 0.73) between the intervention and the control groups, respectively. The oxidative stress was increased; whereas, the sFLT1 expression was not increased when the SRUPP group was compared with controls.

Discussion

SRUPP is associated with an increase in maternal MAP and oxidative stress and therefore it may become a useful tool in the study of pregnancy-related hypertensive disorders.

Introduction

Hypertension is one of the most common medical disorders in pregnancy and it is responsible for an important proportion of maternal adverse outcomes including maternal death [1], [2]. Hypertensive disorders complicate 5–10% of all pregnancies [3]. Many efforts have been made to recreate a preeclampsia-like state in animals, with the aim of allowing researchers to study the pathophysiology of this disease and develop new therapeutic strategies [4], [5]. The reduced uterine perfusion pressure (RUPP) model in rats has been used extensively and it closely mimics many of the characteristics of preeclampsia, including, systemic and renal vasoconstriction, hypertension, immune system abnormalities, oxidative stress, and intrauterine growth restriction [4]. However, its methodology involves placement of clips or ligatures at the level of the abdominal aorta [5], [6], [7], [8], which not only reduces the perfusion pressure to the uterus but it affects other organs as demonstrated by Sholoock et al. [9]. We hypothesize that restricting the reduction of perfusion pressure to the uterus would better simulate the pathophysiology of hypertensive disease of pregnancy. Therefore, the objective of this study was to determine whether selective reduction of perfusion pressure (SRUPP) to the uterus in pregnant rats would induce a hypertensive state with proteinuria, oxidative stress and intrauterine growth restriction. In addition we investigated the effect of SRUPP on placental angiogenic signaling.

Section snippets

Animal housing and handling

Timed pregnant Sprague–Dawley rats, were received from Harlan Laboratories, Inc., (Indianapolis, IN) and were housed in a temperature-controlled room at 20–26° C on a 12-h light/dark cycle and fed standard rat chow (Teklad 8640, Harland Laboratories, Inc., Indianapolis, IN) ad libitum with tap water to drink. All procedures in this study protocol were approved by the University of Tennessee Health Science Center Animal Care and Use Committee.

Experimental protocol

The animals were divided into two groups of 10 rats

Results

As shown in Table 1, there was no difference in body weight between the SRUPP group and the control group on day 14 of gestation (P = 0.524). The SRUPP rats gained less weight and were significantly smaller than the control rats on day 21 of gestation (P = 0.0009). Mean arterial blood pressure (MAP) in the controls (86 ± 0.9 mmHg) was not different from that of the SRUPP rats (86 ± 0.6 mmHg) on day 14 of gestation (P = 0.9891). On day 21 of gestation MAP in the SRUPP group was 109 ± 1.7 mmHg

Discussion

A selective reduction of perfusion pressure to the uterine circulation is associated with a significant increase in maternal mean arterial blood pressure and oxidative stress but with no significant change in urinary protein excretion or placental sFLT1 mRNA expression.

Many researchers have tried to explain how preeclampsia develops and after many attempts today we still have a lack of understanding of the entire pathologic process of this disease. The predominant hypothesis about the

Conflict of interest

The authors report no conflict of interest.

Acknowledgment

We would like to acknowledge Wenyuan Zhao M.D., Ph.D., for important contributions in laboratory methods and work. We are also indebted to Jim Wan, Ph.D., for his contribution to the statistical analysis.

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    Present address: Texas Tech University Health Sciences Center at the Permian Basin, Odessa, TX, USA.

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