Gene expression in ductus arteriosus and aorta: comparison of birth and oxygen effects.
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 PGE2 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.
Costa
Mario
M
Institute of Neuroscience, Consiglio Nazionale delle Ricerche, Pisa, Italy.
Barogi
Silvia
S
Socci
Nicholas D
ND
Angeloni
Debora
D
Maffei
Margherita
M
Baragatti
Barbara
B
Chiellini
Chiara
C
Grasso
Emanuela
E
Coceani
Flavio
F
D000465:Algorithms; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000196:embryology / Q000378:metabolism*; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004373:Ductus Arteriosus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D018496:Hyperoxia / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010100:Oxygen / Q000494:pharmacology*; D036801:Parturition / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D003285:Contractile Proteins; D050989:GATA2 Transcription Factor; C494713:Gata2 protein, rat; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010100:Oxygen