| Abstract: |
Ductus arteriosus (DA) closure is initiated by oxygen rise postnatally and progresses in two, functional-to-permanent, stages. Here, using GeneChip Arrays in rats (normoxic and hyperoxic fetus, normoxic newborn), we examined whether oxygen alone duplicates the birth process in affecting DA genes. In addition, by comparing DA with aorta (Ao), we identified features in postnatal gene profile marking transitional adjustments in a closing (DA) vs. a persistent (Ao) vessel. We found changes in neonatal DA denoting enhanced formation and action of the constrictor endothelin-1 (ET-1). Likewise, ANG II type 1 receptor was upregulated, and the compound was a constrictor. Conversely, relaxant PGE 2 became less effective. Among agents for functional closure, only ET-1 was affected similarly by oxygen and birth. Coincidentally, neonatal DA showed enhanced contractile drive with upregulation of Rho-Rho kinase and calcium signaling along with downregulation of contractile proteins. The latter effect was shared by oxygen. Changes denoting active remodeling were also seen in neonatal but not hyperoxic fetal DA. Ao, unlike DA, exhibited postnatal variations in noradrenergic, purinergic, and PGI2 systems with opposing effects on vasomotion. Contraction and remodeling processes were also less affected by birth, whereas lipid and glucose metabolism were upregulated. We conclude that several agents, including ANG II as novel effector, promote functional closure of DA, but only ET-1 is causally coupled with oxygen. Oxygen has no role in processes for permanent closure. Functional closure is associated with downregulation of contractile apparatus, and this may render neonatal DA less amenable to tone manipulation. Conceivably, activation of metabolism in neonatal Ao is a distinguishing feature for transitional adaptations in the permanent vasculature. Copyright © 2006 the American Physiological Society. |
| Keywords: |
nonhuman; genetic analysis; reproducibility of results; animals; gene expression; oxygen; dose-response relationship, drug; algorithms; gene expression regulation; rna, messenger; oligonucleotide array sequence analysis; nucleotide sequence; angiotensin ii; prostaglandin e2; rat; newborn; pregnancy; down regulation; rats; upregulation; fetus; animals, newborn; unindexed sequence; lipid metabolism; birth; rats, long-evans; vasoconstrictor agents; rho kinase; postnatal development; rho factor; glucose metabolism; gata2 transcription factor; calcium signaling; aorta; endothelin 1; prostacyclin; ductus arteriosus; oxygen blood level; hyperoxia; ductus closure; fetal and neonatal physiology; postnatal programming; angiotensin 1 receptor; ductus arteriosus obliteration; noradrenergic system; contractile proteins; parturition; receptor, angiotensin, type 1; vasoconstriction
|
