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The Evaluation of Hypoxia-Inducible Factor 1 in N-Nitro-L-Arginine Methyl Ester Preeclampsia Model of Pregnant Rats
  1. Ali Kaya, MD*,
  2. Abdullah Boztosun, MD,
  3. Hulya Seckin, MD,
  4. Ahmet Sami Guven, MD*,
  5. Zekeriya Kucukdurmaz, MD§,
  6. Sefa Gulturk, MD,
  7. Omer Cevit, MD*
  1. From the Departments of *Pediatrics, †Obstetric and Gynecology, Cumhuriyet University School of Medicine; ‡Department of Pediatrics, Sivas State Hospital; and Departments of §Cardiology and ∥Physiology, Cumhuriyet University School of Medicine, Sivas, Turkey.
  1. Received April 14, 2011, and in revised form May 17, 2011.
  2. Accepted for publication July 18, 2011.
  3. Reprints: Ali Kaya, MD, Çocuk Sağlığı ve Hastalıkları AD, Cumhuriyet Üniversitesi Tıp Fakültesi, 58140 Sivas, Turkey. E-mail: dralikaya{at}
  4. The authors have no conflict of interest to declare.


Objective The objective of the study was to evaluate hypoxia-inducible factor 1 (HIF-1), which plays a major role in the stimulation of angiogenesis in placental tissues, by using immunohistochemical staining in preeclampsia model of rats, developed by N-nitro-L-arginine methyl ester (L-NAME)

Methods Thirty pregnant rats were randomized into 2 groups (n = 15 in each group) on day 10 of gestation. L-NAME was given to rats in the study group by gavage. On days 0, 10, and 20 of gestation, rats were weighted, and urine protein values and blood pressures were measured. Hypoxia-inducible factor 1 expressions were assessed with immunohistochemical staining by using avidin-biotin peroxidase via selecting preparation.

Results Systolic and diastolic blood pressures and urine protein value of L-NAME group on day 20 of gestation were found to be significantly higher than those obtained on days 0 and 10 of gestation in the same group and those obtained on day 20 of gestation in the sham group (P < 0.05). Maternal weight, number of fetuses, and mean fetal weight of rats in L-NAME group on day 20 of gestation were found to be significantly lower than those obtained from rats in the sham group (P < 0.05). Regarding HIF-1 expression of placental tissues, mild immunohistochemical staining was found in 2 rats (13.4%) and moderate in 13 rats (86.6%) in the L-NAME group. A significant difference was found in terms of HIF-1 positivity in the maternal placentas of both groups (P < 0.05).

Conclusions L-NAME preeclampsia model of pregnant rats is consistent with human preeclampsia in terms of hypertension, proteinuria, and intrauterine growth retardation; in addition, it also shows evidence of placental hypoxia findings.

Key Words
  • hypoxia-inducible factor 1
  • preeclampsia
  • rat

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