Effects of selective reduced uterine perfusion pressure in pregnant rats
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.
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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.