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Obstetrics
Endothelin type A receptor antagonist attenuates placental ischemia–induced hypertension and uterine vascular resistance

Presented orally at the 31st Annual Meeting of the Society for Maternal-Fetal Medicine, San Francisco, CA, Feb. 7-12, 2011.
https://doi.org/10.1016/j.ajog.2011.01.049Get rights and content

Objective

We sought to determine the effect of an endothelin type A receptor antagonist (ETA) on uterine artery resistive index (UARI) and mean arterial pressure (MAP) in a placental ischemia rat model of preeclampsia produced by reduction in uterine perfusion pressure (RUPP).

Study Design

UARI was assessed by Doppler velocimetry in RUPP and normal pregnant controls (NP) on gestational days (GD) 12, 15, and 18. UARI was also determined on GD 18 in NP and RUPP pregnant dams after pretreatment with ETA. MAP was recorded on GD 19.

Results

The RUPP group had a higher MAP and UARI on GD 15 and 18 than the NP group. Pretreatment with ETA attenuated both the MAP and GD-18 UARI in the RUPP group without affecting these parameters in the NP group.

Conclusion

The improvement in UARI could be one potential mechanism for the reduction in MAP in response to ETA in pregnant dams with ischemic placentas.

Section snippets

Materials and Methods

Pregnant Sprague-Dawley rats (Harlan Sprague Dawley Inc, Indianapolis, IN) were used in the study. Animals were housed in a temperature-controlled room (23°C) with a 12-/12-hour light/dark cycle. All experimental procedures executed in this study were in accordance with the National Institutes of Health guidelines for use and care of animals. The study protocol was approved by the Institutional Animal Care and Use Committee at the University of Mississippi Medical Center.

Experiments were

Results

The UARI in NP dams was relatively unchanged up to GD 15 and was noted to be lower by GD 18. UARI for the RUPP dams was similar to the untreated controls on GD 12 and rose significantly by the day following treatment and continued to remain higher than the controls on GD 18 (Figure, A). The mean UARI in NP and RUPP groups were 0.59 ± 0.02 vs 0.57 ± 0.01 (P = .423), 0.60 ± 0.02 vs 0.71 ± 0.02 (P < .001), and 0.54 ± 0.03 vs 0.67 ± 0.02 (P < .001) on GD 12, 15, and 18, respectively.

When compared

Comment

The reduction of UARI with increasing gestational age in pregnant dams is similar to that seen in pregnant women16 and perhaps reflects changes in the uterine circulation to accommodate the increasing metabolic demand of the uteroplacental-fetal unit. The rise in UARI in response to induction of chronic placental ischemia associated with the RUPP procedure17, 18 appears to be immediate and sustained over time. Acute cardiovascular changes, including increases in peripheral vascular resistance

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    This work was supported by National Institutes of Health Grant no. HL-51971.

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    Cite this article as: Tam Tam KB, George E, Cockrell K, et al. Endothelin type A receptor antagonist attenuates placental ischemia–induced hypertension and uterine vascular resistance. Am J Obstet Gynecol 2011;204:330.e1-4.

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