Effects of betamethasone on peripheral arterial development in term fetal rabbit.
Glucocorticoids are given antenatally to promote pulmonary epithelial maturation and prevent respiratory distress syndrome in premature newborns. In contrast to airway changes, effects on vessels are less documented. We hypothesized that antenatal betamethasone (BM) administration promotes vascular development. Does received either a course of BM = 0.05 mg/kg/day (18 does, 70 fetuses), BM = 0.1 mg/kg/day (20 does, 75 fetuses), or saline (11 does, 92 fetuses) starting on d25, 26 (canalicular stage), d27, d28 (saccular stage), and d29 (alveolar stage) of gestation. In total 236 fetuses from 49 does were examined at term (d31) in terms of vascular development. Lung specimens were weighed and formalin fixed for morphometry. We determined differences in fetal body, liver and lung weight, proportionate medial thickness, muscularization of intra-acinar vessels, number of vessels under 100 microm, as well as immunoreactivity to Flk-1 in vascular smooth muscle and endothelial cells. A dose-dependent reduction in neonatal body and organ weight was observed in fetuses exposed to BM at d25. In contrast, term liver weight increased after late administration of BM (d28, 29). There was a dose- and time-dependent thinning of the pulmonary arterial media, which coincided with a decreased proportion of intra- and pre-acinar muscularized arteries (ED <or= 60 microm) and increased microvascularization (ED <or= 30), as well as increased endothelial immunoreactivity for Flk-1. Analyzing our data using a purpose designed geometrical model, the results suggest that maternal administration of BM promotes changes in vascular morphology, which may be compatible with remodeling and vessel formation.
Roubliova
Xenia I
XI
Center for Surgical Technologies, Faculty of Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
Lewi
Paul J
PJ
Vaast
Pascal
P
Jani
Jacques C
JC
Verbeken
Eric K
EK
Tibboel
Dick
D
Deprest
Jan A
JA
D000818:Animals; D001623:Betamethasone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005865:Gestational Age; D005938:Glucocorticoids / Q000008:administration & dosage*; D008168:Lung / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects*; D011817:Rabbits; D017540:Tunica Media / Q000187:drug effects
D005938:Glucocorticoids; D001623:Betamethasone