Prolonged inhibition of nitric oxide synthesis in pregnant rats: effects on blood pressure, fetal growth and litter size.

Methods: In order to investigate the effect of chronic inhibition of nitric oxide synthesis along pregnancy, pregnant rats were given drinking water alone (control group) or drinking water containing nonselective nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 15 mg/day/rat equivalent to 50 mg/kg/day; treated group), from postmating days 1 to 18 of pregnancy. On days 1 to 17 of pregnancy, urinary volume, urinary sodium and potassium excretion, and urine protein concentration were measured. Systolic blood pressure (SBP) was recorded daily. On days 6, 11 and 18 of pregnancy the number of sites of implantation, number of embryos, litter size, fetal and placenta weight were determined.

Results: Systolic blood pressure (mmHg) increased (p<0.001) on the 2nd day of administration of L-NAME and remained high throughout the experiment. This treatment increased urinary protein excretion and urine volume (p<0.01), with changes in the sodium and potassium excretion rate along the study. On day 6 of gestation in treated group, the number of implantation sites (0.14+/-0.10) significantly decreased (p<0.05) compared with the control group (1.45+/-0.58), but on day 11 of pregnancy the number of embryos was similar in both groups. By day 18 of pregnancy, L-NAME caused a substantial decrease (p<0.001) in litter weight (6.30+/-0.77 to 12.00+/-0.92 g), weight of placenta (3.17+/-0.22 to 4.74+/-0.21 g) (p<0.001) and litter size (7.95+/-0.59 to 11.95+/-0.45 fetus/litter; p<0.001). Also, treatment with L-NAME caused an important number of fetal resorptions (2.93+/-0.42 No./litter to 0 in control group).

Conclusion: Thus, treatment of pregnant rats with L-NAME, has an important effect on systolic blood pressure and on the physiology of reproduction, mainly in the third stage of pregnancy.