Ontogeny of endothelin-converting enzyme gene expression and protein content in the ovine fetal lung.
Endothelin 1 (ET-1) is a potent vasoconstrictor and smooth muscle comitogen that is produced by endothelin-converting enzyme 1 (ECE-1) in endothelium and smooth muscle of the vascular wall in adult pulmonary arteries. However, little is known about the role of ECE-1 in the fetal pulmonary circulation. The ET-1 protein content falls just prior to birth in the fetal lamb lung. We hypothesized that the expression of ECE-1 is developmentally regulated and that ECE-1 levels fall prior to birth. To test this hypothesis, we measured lung ECE-1 mRNA levels and protein content and determined the cellular localization of ECE-1 expression in lung tissues from fetal lambs between 70 and 140 days of gestation (term = 145 days), newborn lambs, and ewes. We found that ECE-1 mRNA expression and protein content were lower in the fetal lamb lung just prior to birth in comparison with the newborn lamb lung. Immunolocalization of ECE-1 protein showed expression of ECE-1 in the vascular endothelium but not in the vascular smooth muscle at all gestational ages. We conclude that ECE-1 is developmentally regulated and that ECE-1 is expressed in the vascular endothelium but not in the smooth muscle of the fetal pulmonary vasculature. We speculate that alterations in ECE-1 contribute to the changes in ET-1 levels during the perinatal period and that the majority of ET-1 produced in the fetal lamb pulmonary vasculature is produced by the vascular endothelium.
Ivy
Dunbar
D
Pediatric Heart-Lung Center, Section of Pediatric Cardiology, University of Colorado School of Medicine and Children's Hospital, Denver, CO 80218, USA. dunbar.ivy@uchsc.edu
Tanzawa
Kazuhiko
K
Abman
Steven H
SH
D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern / Q000662:veterinary; D015153:Blotting, Western / Q000662:veterinary; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry / Q000662:veterinary; D008168:Lung / Q000201:enzymology* / Q000502:physiology; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012756:Sheep / Q000196:embryology*
D012333:RNA, Messenger; D008666:Metalloendopeptidases