Growth and fertility rates in the offspring of pregnant rats treated with L-ω nitro-L-arginine methyl ester (L-NAME), a nitric oxide inhibitor

Objective: The objective of this study was to determine neonatal growth, fertility, and blood pressure for offspring of pregnant rats following in utero exposure to L-ω nitro-L-arginine methyl ester (L-NAME). Study Design: Osmotic mini-pumps were inserted on day 14 of gestation during the index pregnancy to deliver L-NAME (50 mg/day/rat) or a placebo control continuously. Pup weights were obtained longitudinally until postnatal day 76. Systolic blood pressures were measured on postnatal days 29 and 44. At 11 weeks of age, groups of females and males (control and L-NAME–exposed in utero) were housed in pairs for 14 days; females were assessed for mating with a sperm positive vaginal flush and subsequent establishment of pregnancy. Pup weight and systolic blood pressure are expressed as mean ± standard error of the mean and compared by using the unpaired t test. P< .05 was considered statistically significant. Results: Pups born to L-NAME–treated mothers were significantly smaller than controls (5.2 ± 0.2 g and 6.5 ± 0.1 g, respectively; P< .0001)). These differences persisted even at postnatal day 76. There was no difference in systolic blood pressure between control and L-NAME–exposed pups. Successful mating rates were as follows: 90% (9/10) in control females with control males, 67% (8/12) in control females with L-NAME males, 47% (7/15) in L-NAME females with control males, and 31% (4/13) in L-NAME females with L-NAME males, P = .007 (control versus L-NAME females). Conclusion: The offspring of pregnant rats with in utero exposure to L-NAME (prolonged nitric oxide inhibition) exhibited decreased neonatal weight, postnatal growth, and fertility. (Am J Obstet Gynecol 2002;186:89-93.)