79 Renal and cardiac disturbances 8 weeks after exposure to placental ischemia in rat dams

Abstract

Introduction Women with a history of preeclampsia (PE) have an increased risk to develop cardiovascular and renal disease later in life. Pre-existing cardiovascular risk factors may play an important role, on the other hand the transient presence of placenta ischemia might induce persistent changes in the maternal cardiovascular system. Objective We aimed to assess whether exposure to placental ischemia during pregnancy enhances long-term effects on the maternal cardiovascular and renal systems in rats using the Reduced Uterine Perfusion Pressure (RUPP) model for PE. Methods At gestational day (gd) 14, Sprague Dawley rats were randomized to two groups: SHAM (n = 12) or RUPP (n = 21). The RUPP procedure involved partial clipping of the lower abdominal aorta and both ovarian arteries to reduce placental flow. Post delivery, rats were followed for 8 weeks after which we measured mean arterial pressure (MAP, carotid), GFR (transcutaneous, sinistrin), albuminuria (24-h) and cardiac function (cardiac ultrasound). All rats were sacrificed for tissue collection and mesenteric arteries were used for reactivity experiments to assess peripheral arterial function. Parametric data are presented as mean ± SD and non-parametric data as median (25–75 percentile), and were respectively analyzed with student T-test or Mann–Whitney U-test. Morphologic and transcriptional analyses are ongoing. Results The mean weight gain of the RUPP rats during pregnancy (gd13–gd19) was significantly lower compared to the SHAM operated rats [30 ± 18 g vs 63 ± 12; p Conclusions We show that exposure to experimental placenta ischemia is accompanied by subtle disturbances in maternal cardiac and renal function after recovery from PE. Our results indicate that placental ischemia itself can result in persistent changes in the cardiac and renal systems, although at this early stage no differences in vascular reactivity or blood pressure regulation were observed. Future studies should elucidate whether aging, a second hit or underlying disease aggravate target organ dysfunction after placental ischemia. Results Despite being all followed up for 27.5 yrs, the exposed women were older when they had their first pregnancy with and median age of 24.9 yrs ((5th;95th percentiles) (19.5;27.3)) vs. 24.6 yrs (19.4;27.3), p Conclusion A small extra vitamin D in fetal life from food fortification reduced risk of PE later in life. The effect was mainly seen among current smokers.