Prolonged blockade of nitric oxide synthesis in gravid rats produces sustained hypertension, proteinuria, thrombocytopenia, and intrauterine growth retardation

Am J Obstet Gynecol. 1994 May;170(5 Pt 1):1458-66. doi: 10.1016/s0002-9378(94)70179-2.


Objective: Our purpose was to test the hypothesis that chronic inhibition of nitric oxide synthesis in pregnant rats can produce a preeclampsia-like syndrome.

Study design: Pregnant rats were instrumented on day 14 of gestation (parturition day 21 to 22) and infused continuously through a venous catheter with L-nitro-arginine, a potent inhibitor of nitric oxide synthase, or with sterile saline solution from day 18 until 24 hours post partum. A group of virgin rats was treated identically. Blood pressure was recorded in unrestrained animals with an aortic catheter for 30 minutes before infusion and repeated each day throughout the experiment. Urinary albumin, platelet count, weight of newborn pups, blood chemistry, and several other parameters were determined. Data were analyzed by one-way, repeated-measures analysis of variance, with Dunnett's t test or by Student t test.

Results: Mean arterial pressure increased from 102.6 +/- 2.8 to a mean maximum of 152.5 +/- 7.3 on the second day of infusion and remained in this range until delivery, after which it fell significantly, in spite of continuing infusion of L-nitro-arginine. This treatment increased urinary albumin (milligrams per 24 hours) from 8.3 +/- 1.5 to 56.3 +/- 14.3 in gravid and from 8.2 +/- 0.8 to 18.2 +/- 2.4 in virgin rats. Weight of newborn pups was reduced by L-nitro-arginine from 5.62 +/- 0.10 to 3.37 +/- 0.32 gm (p < 0.005) without affecting time of delivery or litter size. Platelet count was reduced 58% in gravid and 50% in virgin rats.

Conclusion: Chronic inhibition of nitric oxide synthesis in gravid rats leads to sustained hypertension, proteinuria, thrombocytopenia, and intrauterine growth retardation, providing a simple animal model for preeclampsia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Creatinine / urine
  • Female
  • Fetal Growth Retardation / etiology*
  • Hematocrit
  • Hypertension / etiology*
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / antagonists & inhibitors*
  • Platelet Count / drug effects
  • Potassium / urine
  • Pregnancy
  • Pregnancy Complications / etiology*
  • Proteinuria / etiology*
  • Rats
  • Rats, Wistar
  • Sodium / urine
  • Thrombocytopenia / etiology*
  • gamma-Glutamyltransferase / urine


  • Nitric Oxide
  • Arginine
  • Sodium
  • Creatinine
  • gamma-Glutamyltransferase
  • Potassium
  • NG-Nitroarginine Methyl Ester