Characterization of Mild Delayed Gestational Hypertension in Rats Following Ozone Exposure

Abstract

The contribution of air pollution induced cardio-pulmonary damage on the development of hypertensive disorders of pregnancy and other adverse outcomes of pregnancy has gained increased attention as epidemiological data continues to highlight spatiotemporal pregnancy trends related to air pollution exposure. However clinical mechanistic data surrounding gestational complications remains sparse, necessitating the need for the use of animal models to study these types of complications of pregnancy. The current study seeks to examine the real-time effects of mid-gestational ozone exposure on maternal blood pressure and body temperature through the use of radiotelemetry in a rat model. The exposure resulted in acute depression of heart rate and core body temperature as compared to control animals. Ozone exposed animals also presented with a slight but significant increase in arterial blood pressure which was perpetuated until term. The data presented here illustrates the feasibility of murine models to assess cardiovascular complications caused by inhaled toxicants during the window of pregnancy.

Keywords: Air Pollution; Hypertension; Ozone; Pregnancy.

Figure 1

Normalized body weight trends for telemetered rats (third experiment shown) following pairing with male rats. By GD8.5 sufficient discrimination was evident to select and randomize rats for exposures. No differences were seen with O₃ exposure

Figure 2

Mean arterial blood pressure from pregnant rats (n=7/grp) exposed to filtered air (control) or 1 ppm O₃ for 4h on GD10.5. Shown are (A) raw data (10 minute collections, averaged by group); (B) 24h average data; and (C) data normalized to average readings from GD3.5–GD8.5, a period where handling was minimized and pairing with male rats was complete. Data normalization in (C) was conducted to offset initial group differences apparent in the raw data (A and B). Asterisks indicate significant difference between the FA and O₃ groups, based on a 2-way repeated measures ANOVA with Šídák’s post-hoc testing (*p<0.05; **p<0.01; ***p<0.001) using GraphPad Prism

Figure 3

Physical activity (A), heart rate (B), core body temperature (C) for the full 22 day period of pregnancy, and more detailed resolution of core body temperature relative to exposure (D) from pregnant rats (n=7/grp) exposed to filtered air (control) or 1 ppm O₃ for 4h on GD10.5. Asterisks indicate significant difference between the FA and O₃ groups, based on a 2-way repeated measures ANOVA with Šídák’s post-hoc testing (*p<0.05) using GraphPad Prism

Figure 4

Summarizing studies from our laboratory and others, we propose that inhaled pollutants such as ozone can promote or exacerbate gestational by causing circulating factors arising from the lung that retard placental angiogenesis, which ultimately leads to placental insufficiency later in pregnancy. Figure created using Biorender.