Lung Endothelin Gene Expression does not Change with Oligohydramnios-Induced Pulmonary Hypoplasia 1626

Angiogenesis is regulated by many factors resulting in the formation of new blood vessels. Several known growth factors are implicated in this process. There is evidence that endothelin-1 (ET-1) may enhance angiogenesis and vascular remodeling, either by direct stimulation of smooth muscle cell proliferation or indirectly by stimlation of smooth muscle cell production of vascular endothelial growth factor (VEGF). Thus ET-1 may be an important modulator of angiogenesis. Pulmonary hypoplasia is one of several conditions associated with decreased vascularity. The most common etiology for pulmonary hypoplasia is oligohydramnios. We hypothesize that ET-1 expression decreases in states of lung hypoplasia. We examined the effect of oligohydramnios-induced pulmonary hypoplasia on lung ET-1 expression in late-gestation fetal (21 day) rats. Oligohydramnios was created at 15 day gestation by surgically visualizing the uterine horns and making a unilateral transuterine puncture, allowing for ongoing loss of amniotic fluid. The fetuses in the remaining uterine horn served as the sham-operated controls. Pulmonary hypolasia was assessed by comparing lung and animal weights. Following total RNA isolation from lung homogenates, ET-1 mRNA levels were assessed by a semi-quantitative RT-PCR assay. The house keeping gene malate dehydrogenase was used as an internal control. The lung to body weight ratios were significantly different between the two groups (Sham 0.20 +/-.008; oligo group 0.16 +/- 006; p value 0.02). In contrast to our hypothesis, in this model of decreased vasculogenesis there was no significant difference in ET-1 expression (Sham 0.302 +/-.06; Oligo group 0.290 +/-.06; p value 0.1293; n=5 paired litter mates from five separate dams). Despite these results we can not conclude that ET-1 has no role in the decreased vascularity found in lung hypoplasia. Several modulators of ET-1 activity may complicate the findings of this study. Such modulators include: the multiple endothelin receptors(ET_A and ET_B), multiple isomers of endothelin (ET-2 and ET-3) and the presence of the endothelin converting enzyme. Evaluation of these ET-1 modulators will help delineate the overall endothelin contribution to the decreased vasculogenesis in pulmonary hypoplasia.