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 pregnancy. Pregnant Sprague-Dawley rats were randomly assigned to a control group (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 systolic pressure was measured. On day 21 blood samples were taken for plasma volume, hematocrit, and hormonal measurements. Fetal and placental weights also were determined. Systolic pressure was significantly higher 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 controls (21.5 +/- 0.8 mL). Both experimental groups had increased hematocrit levels. Plasma renin activity was significantly lower in the experimental groups (11.5 +/- 3 and 7.2 +/- 1.5 ng angiotensin I/mL per hour) than in controls (21.9 +/- 2.7 ng angiotensin I/mL per hour); however, no changes 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 experimental groups. In conclusion, the present data indicate that long-term N omega-nitro-L-arginine administration to pregnant rats leads to increased blood pressure, reduced plasma volume expansion, lower plasma renin activity, and fetal growth retardation.(ABSTRACT TRUNCATED AT 250 WORDS)
D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D005314:Embryonic and Fetal Development / Q000187:drug effects / Q000502:physiology; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology; D005333:Fetus / Q000187:drug effects; D005865:Gestational Age; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D010953:Plasma Volume; D011247:Pregnancy / Q000187:drug effects / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D013997:Time Factors; D014664:Vasodilation / Q000502:physiology
D019335:Nitroarginine; D009569:Nitric Oxide; D000450:Aldosterone; D001120:Arginine; D019001:Nitric Oxide Synthase; D012083:Renin