EFFECTS OF LONG-TERM NITRIC-OXIDE SYNTHESIS INHIBITION ON PLASMA-VOLUME EXPANSION AND FETAL GROWTH IN THE PREGNANT RAT

We conducted the present study to investigate whether the vasodilator nitric oxide plays a role in plasma volume homeostasis during pregnanc y. Pregnant Sprague-Dawley rats were randomly assigned to a control gr oup (n = 18) or to groups receiving 0.69 mmol/L (n = 11) or 1.7 mmol/L (n = 14) N-omega-nitro-L-arginine, a competitive inhibitor of nitric oxide synthetase, from gestational days 7 through 21. On day 20 systol ic pressure was measured. On day 21 blood samples were taken for plasm a volume, hematocrit, and hormonal measurements. Fetal and placental w eights also were determined. Systolic pressure was significantly highe r in experimental rats (101+/-6 and 115+/-6 mm Hg in the 0.69 and 1.7 mmol/L groups, respectively) than in controls (79.7+/-7.5 mm Hg), and plasma volume was lower (18.4+/-1.1 and 17.1+/-0.5 mL) than in control s (21.5+/-0.8 mL). Both experimental groups had increased hematocrit l evels. Plasma renin activity was significantly lower in the experiment al groups (11.5+/-3 and 7.2+/-1.5 ng angiotensin I/mL per hour) than i n controls (21.9+/-2.7 ng angiotensin I/mL per hour); however, no chan ges were observed in aldosterone levels. Experimental groups had lower fetal weight (4.6+/-0.1 and 5.1+/-0.1 g) than controls (5.5+/-0.1 g). In addition, fetal hindlimb hypoplasia was observed in the experiment al groups. In conclusion, the present data indicate that long-term N-o mega-nitro-L-arginine administration to pregnant rats leads to increas ed blood pressure, reduced plasma volume expansion, lower plasma renin activity, and fetal growth retardation. These results suggest that ni tric oxide may play an important role in maternal systemic vasodilatat ion and indirectly in plasma volume homeostasis and fetal growth.