Infants with intrauterine growth restriction (IUGR) are at high risk for morbidity and mortality. Preeclampsia, one of the leading causes of IUGR, begins during the canalicular phase of lung development. The aim of our study was to determine whether induced IUGR was responsible for abnormal lung development in rat pups. We randomized pregnant Sprague-Dawley rats to daily gavage with either the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME; n ϭ 5, 50 mg · kg Ϫ1 · dϪ1 ) or pure water (n ϭ 6). The pups were weighed at birth and on postnatal days 7 and 14. At each of these time points, pups were killed and their lung growth was assessed on the basis of lung volume and light-microscopy morphometric data. At birth, body weight, total alveolar surface area, and alveolar surface density were significantly decreased and alveolar size was significantly increased in the L-NAME group, compared with the control group. On day 7, body weight was similar in the two groups, and the only significant difference was smaller total alveolar surface area in the L-NAME group. On day 14, neither body weight nor lung morphometric parameters were significantly different between the L-NAME group and the controls. These results suggest that postnatal catch-up growth may completely correct the lung development disorders present at birth in IUGR pups, in parallel with the catch-up body weight gain. Studies have established that intrauterine growth restriction (IUGR) is correlated with increased morbidity and mortality (1-3). Despite the huge strides made in neonatal medicine over the past 15 y, the risk for respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis, as well as length of stay and hospital costs, remain higher in growth-restricted newborns (3). Importantly, the adverse effects of IUGR are long lasting, one of the most common long-term consequences being respiratory disease (4 -7).Preeclampsia is among the leading causes of IUGR. The placental vascular abnormalities associated with preeclampsia impair maternofetal exchanges, thereby restricting fetal growth (8). Impairments in maternofetal exchanges begin during the third trimester of pregnancy, during which lung development is at the canalicular phase, characterized by formation of the distal airways, blood vessels, and alveolar-capillary barrier (9).Although the pathophysiology of preeclampsia remains unclear, experimental evidence points to a key role for nitric oxide (NO) (10 -13). NO synthase (NOS) inhibition during the last third of pregnancy in rats was followed by hypertension and proteinuria in the dams and by IUGR and high fetal mortality in the offspring, a combination that replicated preeclampsia in humans (14 -16). In rats, IUGR induced by NOS inhibition was associated with hindlimb necrosis at birth (17). To our knowledge, the long-term development of the offspring was not documented. These data prompted us to assess whether lung development was impaired in rat pups with IUGR induced by NOS inhibition in the ...