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19 EVIDENCE OF OXIDATIVE STRESS IN A RAT MODEL OF PREECLAMPSIA.
  1. S. D. Danchuk,
  2. J. Denson,
  3. Y. Hong,
  4. J. B. Puschett
  1. Department of Medicine, Section of Nephrology, Tulane University School of Medicine, New Orleans, LA

Abstract

We have developed a rat model of preeclampsia related to the administration to pregnant animals of desoxycorticosterone acetate (DOCA) and the replacement of their drinking water with 0.9% saline. At 16-19 days of gestation, the rats demonstrate established hypertension, proteinuria, and intrauterine growth restriction (IUGR). Oxidative stress has been reported in various hypertensive models and is considered to play an important role in the pathogenesis of some of the clinical features of preeclampsia. Accordingly, we have studied the urinary excretion of 8-isoprostane (8-IP), an indicator of the oxidative process. Pregnant Sprague-Dawley rats (250-300 g) were rendered “preeclamptic” (PDS, n = 7). Determinations were performed prior to pregnancy and at 16-19 days of gestation. Their blood pressures (BPs), 24-hour protein, and 8-IP excretion in urine and pup numbers for PDS rats were compared to those of normal pregnant animals (NP, n = 6). BP, obtained with a tail cuff method, increased in the PDS rats from a baseline level of 114 ± 3 to 136 ± 2 mm Hg (p < .001). BP in the NP rats fell from a mean baseline value of 117 ± 3 to 108 ± 5 mm Hg (p < .05), nearing the end of gestation, much as is the case in the course of human pregnancy. Urinary protein excretion was higher in PDS than in NP animals (18.6 ± 3.6 and 4.0 ± 0.3 mg protein/24 h, respectively, p < .001) at the end of gestation. Pup number was 8 ± 1 in the PDS rats, which differed significantly (p < .005) from the corresponding value for the NP animals (15 ± 1). In addition, malformed pups were common in the PDS rats but were not seen in the NP animals. Urinary 8-IP excretion increased from 10.0 ± 1.6 to 16.5 ± 2.3 pg/min (p < .05) in the PDS rats. The mean excretion rates in the NP animals did not change significantly (p > .05) from prepregnancy to late gestation periods (6.6 ± 0.6 and 9.3 ± 1.3 pg/min, respectively). Based upon these data, we conclude that oxidative stress is a feature of a rat model of preeclampsia as it is in the human condition.

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