Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Abstract 387Developmental Pharmacology: Drug Effects on Neonatal Angiogenesis and Vascular Function Platform, Monday, 5/3
Normal lung growth and development involves multiple and interactive signals that coordinate growth between airways and vessels. In the rat, alveolarization occurs primarily during the first 3 weeks of postnatal life. Past studies have demonstrated that adverse stimuli, such as hypoxia, hyperoxia, and dexamethasone treatment, can disrupt lung growth during this critical period, causing lung hypoplasia with reduced alveolarization. Normal lung vascular growth during this time period occurs primarily by angiogenesis, concomitant with alveolar development. However, mechanisms that link vascular development with alveolarization are unclear. To determine if angiogenesis is necessary for normal alveolarization, we hypothesized that inhibition of angiogenesis would disrupt normal lung growth and alveolarization. To test this hypothesis, we studied the effects of 2 anti-angiogenic agents, fumagillin and thalidomide, on alveolarization in infant rats. Newborn Sprague-Dawley rats were treated with daily injections of fumagillin (2 mg/kg; subcutaneous), thalidomide (10 mg/kg; intraperitoneal), or vehicle (control; DMSO). Injections were initiated on day 1 and continued for 13 days. Rats were sacrificed on day 14 for study. Lungs were formalin fixed at constant pressure (10 cm H2O), paraffin-embedded, sectioned and stained for histology and morphometric analysis. Tissue analysis was performed after masking of the treatment group from the observer. Alveolarization was assessed by radial alveolar counts (RAC); vessel density was expressed as the number of vessels per high powered field. We found that fumagillin and thalidomide treatment reduced RAC in comparison with vehicle controls. Vessel density was reduced in the fumagillin-treated group but not in the thalidomide-treated rats. (see table; * signifies p<0.05 versus vehicle control group).
Jakkula, M., Le Cras, T. & Abman, S. Effects of Fumagillin and Thalidomide Treatment on Alveolarization in the Developing Rat Lung.
Pediatr Res45, 67 (1999). https://doi.org/10.1203/00006450-199904020-00404
