Endothelin-1 (ET-1), a potent vasoconstrictor and smooth muscle mitogen, is produced from its precursor, preproendothelin-1 (ppET-1). In the late-gestation fetal lung, the effects of ET-1 are dependent upon stimulation of ET-A and ET-B receptors, which mediate vasoconstriction and vasodilation, respectively. Physiologic studies in the late gestation fetus have suggested that ET-1 contributes to high pulmonary vascular resistance through the ET-A receptor. However, little is known of the role of the endothelin system earlier in gestation. To further study the role of ET-1 in the developing fetal lung, we studied expression of mRNA for ppET-1 and the ET-A and ET-B receptors from 70-140 days gestation (term = 147 days) as well as the newborn lamb and postpartum ewe. Total RNA was isolated from whole lung tissue and subjected to Northern blot analysis (n=48). mRNA signals were normalized to 18S rRNA levels. We found that ppET-1 mRNA expression decreased from 70 to 113 days, and then peaked at 130 days (p<0.05, Figure). Expression of the ET-A and ET-B receptor mRNAs peaked at 135 and 125 days gestation, respectively, and then decreased in the adult. We conclude that mRNA expression of ppET-1 and the ET receptors is present during early gestation and peaks at late gestation. We speculate that ET-1 may have mitogenic effects, in addition to its effects on vascular tone, during early gestation in the fetal lung.

figure 1

Figure 1