Inhibition of nitric oxide synthesis in rats during pregnancy produces signs similar to those of preeclampsia

Abstract

Preeclampsia is associated with hypertension, fetal growth retardation, and proteinuria. We hypothesized that impaired vascular nitric oxide synthesis during pregnancy may be an important causal factor in preeclampsia. An inhibitor of nitric oxide synthase, L-nitro-arginine methyl ester, or a nitric oxide donor, nitroglycerin, was infused subcutaneously to rats at a constant rate from day 17 of gestation. Systolic blood pressure, day of spontaneous delivery, weight, and mortality rate of pups were recorded. Systolic blood pressures in rats infused with L-nitro-arginine methyl ester at daily doses of both 25 and 50 mg were significantly elevated compared with controls. This treatment also caused a substantial decrease in the weight of pups, with an increase in mortality rate, without affecting the gestational length. These effects were dose dependent. Nitroglycerin infusion, on the other hand, affected neither the weight and mortality rate of the pups nor the length of gestation. Infusion of an inhibitor of nitric oxide synthesis during pregnancy causes hypertension and fetal growth retardation, without affecting gestational length. These signs are similar to those of preeclampsia and indicate that an alteration in nitric oxide synthesis may be one of the factors responsible for this disorder. Treatment with nitric oxide inhibitors may be used in an animal model for preeclampsia, to test various therapeutic strategies.