The chicken embryo as a model for ductus arteriosus developmental biology: cracking into new territory
2006; American Physiological Society; Volume: 292; Issue: 1 Linguagem: Inglês
10.1152/ajpregu.00654.2006
ISSN1522-1490
AutoresGopinath Sutendra, Evangelos D. Michelakis,
Tópico(s)Animal Genetics and Reproduction
ResumoENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGYThe chicken embryo as a model for ductus arteriosus developmental biology: cracking into new territoryGopinath Sutendra, and Evangelos D. MichelakisGopinath Sutendra, and Evangelos D. MichelakisPublished Online:01 Jan 2007https://doi.org/10.1152/ajpregu.00654.2006This is the final version - click for previous versionMoreSectionsPDF (195 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat the ductus arteriosus (DA) is a vital component of the fetal circulation diverting blood flow away from the pulmonary circulation and the nonventilated lungs, directly into the aorta. With the first breath at birth increasing O2 levels in the blood, the DA constricts, now allowing the blood to flow into the expanded and ventilated lungs, marking the transition from fetal to adult circulation. Failure to achieve closure results in an extracardiac shunt, cyanosis, and failure to thrive; this persistent DA (PDA) occurs in about 70% of preterm babies and has an overall incidence of 1/2,000 live births, i.e., it is relatively common (6). Since vasodilating prostaglandins (PGs) are important regulators of human DA tone, cyclooxygenase (COX) inhibitors are often used to close the PDA, and when this fails, surgical measures have to be taken (5). Conversely, in certain types of congenital heart disease, where maintenance of the fetal circulation is desired until corrective surgery, the DA is prevented from closing by infusion of PGs (8). Although relatively effective, both the COX inhibitors and the systemic PG infusion have many undesired effects due to lack of selectivity for the DA. Therefore, an understanding of the mechanisms that regulate vascular tone in the DA, its response to O2, and its developmental biology have significant and direct clinical significance.The DA belongs to a specialized system of O2-sensitive organs and tissues in the body that includes the pulmonary arteries, the carotid body, and the neuroepithelial body among others, which share striking similarities in the ways they respond to changes in O2 tension (25). Therefore, advancing our knowledge on the vascular biology of the DA is important for our understanding of the mechanisms by which cells or blood vessels respond to changes in O2; this has far reaching implications for diverse conditions like ischemia or cancer vascular biology.Significant progress in our understanding of the DA pathobiology has been achieved with the use of animal models, including the sheep (14, 15), the rabbit (18, 22, 23), or primates (20). Few reports have also used human DAs, obtained at the time of complex corrective surgery for congenital heart disease (16, 17). An evolving proposed mechanism for DA closure includes an acute phase, in which within minutes of exposure to normal O2 levels, the DA (which normally exists in hypoxic conditions in the fetus) constricts. This mechanism is thought to be intrinsic to the DA smooth muscle cells (DASMC) (9, 12) and, at least in the human or rabbit DA, includes a sensor (i.e., the electron transport chain of the mitochondria), which changes the production of activated oxygen species (AOS; like H2O2) in response to changes in O2 levels (Fig. 1). This mediator (i.e., the freely diffusible H2O2) can reach the cell membrane and decrease the opening of O2- and redox-sensitive voltage-dependent K+ (Kv) channels (like Kv1.5, Kv2.1, etc.). This causes DASMC depolarization; opening of the voltage-gated Ca2+ channels, increase in intracellular Ca2+ concentration, and vasoconstriction (16, 17, 23). This mitochondria-AOS-K+ channel axis is the basis of O2 sensing in many other O2-sensitive tissues (reviewed in Ref. 25), suggesting that its central role might be preserved during evolution.This acute phase is followed by a subacute phase in which the production of endothelin (and other endothelium-derived modulators) is altered (7, 16, 20), further promoting and sustaining constriction, leading to a functional DA closure. In a more chronic phase (i.e., days) significant changes in the DA vascular wall, including endothelial and DASMC proliferation, extracellular matrix remodeling, or vasa vasora constriction (2, 3, 11, 15) (reviewed in Ref. 6) complete the structural remodeling of the DA and lead to complete, anatomical closure. None of these theories has reached the bedside yet. Furthermore, developmental changes have been described in the elastic laminae (27), Kv channel pathways (22), PG axis, and others (6) that take place prior to birth, “preparing the DA” for its appropriate response upon exposure to normal O2 levels. However, if the fetus is born prematurely, these changes are incomplete and prevent the normal DA response at birth.An important limitation in our knowledge of these O2 sensing systems and their developmental regulation is the complexity of the available models. All of these include mammals, where the fetal/placental circulation has to be exposed to intervention only through complex surgery; manipulation of the ambient O2 levels affect both the mother and the fetus and the duration of pregnancy is long (31 days for rabbit, 141–151 days for sheep). Therefore, there is a need for additional models addressing these limitations.The work by Ågren et al. (1) comes to fulfill this need. The authors used the chicken (Gallus gallus) embryo model to study DA biology. They characterized the basic vascular reactivity and response to O2 in the chicken DA, as well as developmental changes prior to term birth. While at 15 days of gestation (5–6 days prior to pecking) the DA does not yet constrict to O2; it constricts in response to K+ channel inhibition, a pathway that is augmented later in development. On day 19, the magnitude of the constriction to O2 is similar to KCl, a drug that inhibits the gradient of K+ efflux out of DASMC, i.e., functionally inhibiting all K+ channels. In addition, while there is contraction to O2 in DAs preconstricted to norepinephrine, there is no additional contraction in DAs preconstricted with KCl, suggesting that the constriction to O2 involves the closure of K+ channels. Pharmacological dissection of the response to KCl, revealed that the predominant K+ channels are 4-aminopyridine- (and not glyburide or tetra-ethylammonium-) sensitive; in other words, they belong to the family of Kv channels (and not the KATP or KCa channels). The augmentation of the response to 4-aminopyridine and O2 toward pecking was similar, suggesting that the two mechanisms are similarly regulated, or they represent a single system. Specific O2-sensitive Kv channels, like Kv1.5 and Kv2.1, have been shown to be the effectors of O2-constriction in the human DA (16, 17, 22, 23). Interestingly, the developmental regulation of Kv channel expression that has recently been described in DA (22), resembles the one implied by the authors’ work in the chicken. In human and rabbit DA, Kv channel expression increases toward term delivery and the weak response to O2 in premature (and Kv-poor) DA can be rescued by gene transfer of Kv1.5 or Kv2.1 (22).In another intriguing similarity to human DA (16) (Figure 1), the constriction to O2 was not significantly affected by the presence of an NO synthase and an endothelin receptor blocker, in keeping with the observation that the predominant mechanism in acute O2 constriction involves Kv channel inhibition. However, in contrast to human DA, the chicken DA was completely unresponsive to several COX inhibitors. This suggests that the Kv channel mechanism might have preceded the PG mechanisms in evolution.The chicken is believed to be a descendent of the Archaeopteryx, a dinosaur from the Jurassic period over 150 million years ago (4). The draft sequence of the chicken genome consists of ∼20,000–23,000 genes (10), which is comparable to the human genome (13). Approximately 60% of the chicken protein-coding genes have a single human orthologue (10). As we discussed above, the similarities between the chicken and the human DA are striking, suggesting that the Kv channel inhibition in response to O2 is preserved during evolution; and that there might also be similar developmental regulatory mechanisms. The authors suggest that, like in humans, one or more Kv channels are the effectors in O2-induced DA constriction. It is striking that the critical parts for the function of Kv1.5, i.e., the voltage sensor and the pore of the channel, show a remarkable similarity in terms of sequence across birds, worms, flies, and humans and are identical between the human and chicken (Fig. 1).The chicken egg may be a good model for studying the fetal circulation, as the chicken embryo can be manipulated quite easily in exposing it to different experimental conditions, such as hypoxia (24). This condition can be directly related to the developmental physiology of a human fetus confined to a uterus with a poorly developed placenta resulting in a relatively hypoxic environment. Establishing a similar environment in a mammalian model would confine the mother to a hypoxic chamber, and the relative Po2 of the fetus may still be varied to that of the mother; the fetal organs might also be exposed to maternal-derived circulating factors, released in response to environmental stress. Additionally, the lung development that is also dysregulated in prematurity can also be studied in this model (21). Important questions that need to be answered include: 1) what is the molecular identity of the chicken DASMC Kv channels; 2) do isolated chicken DASMC show Kv channel inhibition (patch clamping) to O2 and do they respond in an opposing manner compared to the pulmonary artery smooth muscle cells, which are inhibited by hypoxia in all mammals (25); and 3) is a mitochondria or other redox-based mechanism involved in this response?If these studies show similarities to the mammalian and human DA, then a new model will be available for translational studies for the human DA and, moreover, to the biology of vascular O2 sensing in vivo. The egg-chicken model will be easier to manipulate (for example, expose the whole egg into a hypoxic chamber), or intervene on [easily inject drugs (19) or gene therapies (26) through small holes in the eggshell]. Advances in imaging studies will also allow the direct imaging of vascular structures, lungs, and hearts of the chicken embryo before birth. A glimpse into the future is the CT scan image of a 17-day-old chicken embryo in the egg, where the bone structures are seen and the brain and lungs are 3D-reconstructed and shown in blue and red, respectively, in Fig. 1. Looking at this image, one cannot fail to visualize a “baby dinosaur egg” from…“Jurassic Park.” Looking into mechanisms preserved during evolution of O2 sensing from the past might allow us to look into the future of translational developmental vascular biology. Fig. 1.A: CT scan image of a 17-day-old chicken embryo within an intact egg. A part of the egg shell is shown on top of the image. 3-D reconstruction of the bone structures is seen. In addition, 3-D reconstruction of the lungs (red) and brain (blue) was performed. A Gamma Medica (Northridge, CA) rodent SPECT-CT (FLEX preclinical platform) and the Amira software package was used. B: the presence of Nω-nitro-l-arginine methyl ester (l-NAME), meclofenamate, as well as endothelin (ET) receptor and ET converting enzyme inhibitors, do not affect the constriction of human ductus arteriosus (DA) to O2, which is similar in magnitude to the constriction to the voltage-dependent K+ (Kv) channel blocker 4-aminopyridine (4-AP). C: a proposed pathway for the DA constriction. D: striking similarities in the gene regions that encode Kv1.5 pore and voltage sensor in multiple species; the critical-for-function areas are highlighted ( http://searchlauncher.bcm.tmc.edu/multi-align/multi-align.html). NO, nitric oxide, [Ca2+]i, intracellular Ca2+ concentration. [B from: Michelakis (16)].Download figureDownload PowerPointREFERENCES1 Ågren P, Cogolludo AL, Kessels CG, Pérez-Vizcaíno F, De Mey JG, Blanco CE, Villamor E. Ontogeny of chicken ductus arteriosus response to oxygen and vasoconstrictors. Am J Physiol Regul Integr Comp Physiol 292: R485–R496, 2007.Link | ISI | Google Scholar2 Boudreau N, Rabinovitch M. Developmentally regulated changes in extracellular matrix in endothelial and smooth muscle cells in the ductus arteriosus may be related to intimal proliferation. Lab Invest 64: 187–199, 1991.PubMed | ISI | Google Scholar3 Boudreau N, Turley E, Rabinovitch M. Fibronectin, hyaluronan, and a hyaluronan binding protein contribute to increased ductus arteriosus smooth muscle cell migration. Dev Biol 143: 235–247, 1991.Crossref | PubMed | ISI | Google Scholar4 Burish MJ, Kueh HY, Wang SS. Brain architecture and social complexity in modern and ancient birds. Brain Behav Evol 63: 107–124, 2004.Crossref | PubMed | ISI | Google Scholar5 Clyman RI. Ibuprofen and patent ductus arteriosus. N Engl J Med 343: 728–730, 2000.Crossref | PubMed | ISI | Google Scholar6 Clyman RI. Mechanisms regulating the ductus arteriosus. Biol Neonate 89: 330–335, 2006.Crossref | PubMed | Google Scholar7 Coceani F, Kelsey L. Endothelin-1 release from lamb ductus arteriosus: relevance to postnatal closure of the vessel. Can J Physiol Pharmacol 69: 218–221, 1991.Crossref | PubMed | ISI | Google Scholar8 Coceani F, Olley PM. The response of the ductus arteriosus to prostaglandins. Can J Physiol Pharmacol 51: 220–225, 1973.Crossref | PubMed | ISI | Google Scholar9 Fay FS. Guinea pig ductus arteriosus. I. Cellular and metabolic basis for oxygen sensitivity. Am J Physiol 221: 470–479, 1971.Link | ISI | Google Scholar10 Hillier LW, Miller W, Birney E, Warren W, Hardison RC, Ponting CP, Bork P, Burt DW, Groenen MA, Delany ME, Dodgson JB, Chinwalla AT, Cliften PF, Clifton SW, Delehaunty KD, Fronick C, Fulton RS, Graves TA, Kremitzki C, Layman D, Magrini V, McPherson JD, Miner TL, Minx P, Nash WE, Nhan MN, Nelson JO, Oddy LG, Pohl CS, Randall-Maher J, Smith SM, Wallis JW, Yang SP, Romanov MN, Rondelli CM, Paton B, Smith J, Morrice D, Daniels L, Tempest HG, Robertson L, Masabanda JS, Griffin DK, Vignal A, Fillon V, Jacobbson L, Kerje S, Andersson L, Crooijmans RP, Aerts J, van der Poel JJ, Ellegren H, Caldwell RB, Hubbard SJ, Grafham DV, Kierzek AM, McLaren SR, Overton IM, Arakawa H, Beattie KJ, Bezzubov Y, Boardman PE, Bonfield JK, Croning MD, Davies RM, Francis MD, Humphray SJ, Scott CE, Taylor RG, Tickle C, Brown WR, Rogers J, Buerstedde JM, Wilson SA, Stubbs L, Ovcharenko I, Gordon L, Lucas S, Miller MM, Inoko H, Shiina T, Kaufman J, Salomonsen J, Skjoedt K, Wong GK, Wang J, Liu B, Wang J, Yu J, Yang H, Nefedov M, Koriabine M, Dejong PJ, Goodstadt L, Webber C, Dickens NJ, Letunic I, Suyama M, Torrents D, von Mering C, Zdobnov EM, Makova K, Nekrutenko A, Elnitski L, Eswara P, King DC, Yang S, Tyekucheva S, Radakrishnan A, Harris RS, Chiaromonte F, Taylor J, He J, Rijnkels M, Griffiths-Jones S, Ureta-Vidal A, Hoffman MM, Severin J, Searle SM, Law AS, Speed D, Waddington D, Cheng Z, Tuzun E, Eichler E, Bao Z, Flicek P, Shteynberg DD, Brent MR, Bye JM, Huckle EJ, Chatterji S, Dewey C, Pachter L, Kouranov A, Mourelatos Z, Hatzigeorgiou AG, Paterson AH, Ivarie R, Brandstrom M, Axelsson E, Backstrom N, Berlin S, Webster MT, Pourquie O, Reymond A, Ucla C, Antonarakis SE, Long M, Emerson JJ, Betran E, Dupanloup I, Kaessmann H, Hinrichs AS, Bejerano G, Furey TS, Harte RA, Raney B, Siepel A, Kent WJ, Haussler D, Eyras E, Castelo R, Abril JF, Castellano S, Camara F, Parra G, Guigo R, Bourque G, Tesler G, Pevzner PA, Smit A, Fulton LA, Mardis ER, Wilson RK; International Chicken Genome Sequencing Consortium. Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432: 695–716, 2004.Crossref | PubMed | ISI | Google Scholar11 Kajino H, Chen YQ, Seidner SR, Waleh N, Mauray F, Roman C, Chemtob S, Koch CJ, Clyman RI. Factors that increase the contractile tone of the ductus arteriosus also regulate its anatomic remodeling. Am J Physiol Regul Integr Comp Physiol 281: R291–R301, 2001.Link | ISI | Google Scholar12 Kovalcik V. The response of the isolated ductus arteriosus to oxygen and anoxia. J Physiol 169: 185–197, 1963.Crossref | PubMed | ISI | Google Scholar13 Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann N, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blocker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey A, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowski J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ; International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 409: 860–921, 2001.Crossref | PubMed | ISI | Google Scholar14 Levin M, Goldbarg S, Lindqvist A, Sward K, Roman C, Liu BM, Hulten LM, Boren J, Clyman RI. ATP depletion and cell death in the neonatal lamb ductus arteriosus. Pediatr Res 57: 801–805, 2005.Crossref | PubMed | ISI | Google Scholar15 Mason CA, Bigras JL, O’Blenes SB, Zhou B, McIntyre B, Nakamura N, Kaneda Y, Rabinovitch M. Gene transfer in utero biologically engineers a patent ductus arteriosus in lambs by arresting fibronectin-dependent neointimal formation. Nat Med 5: 176–182, 1999.Crossref | PubMed | ISI | Google Scholar16 Michelakis E, Rebeyka I, Bateson J, Olley P, Puttagunta L, Archer S. Voltage-gated potassium channels in human ductus arteriosus. Lancet 356: 134–137, 2000.Crossref | PubMed | ISI | Google Scholar17 Michelakis ED, Rebeyka I, Wu X, Nsair A, Thebaud B, Hashimoto K, Dyck JR, Haromy A, Harry G, Barr A, Archer SL. O2 sensing in the human ductus arteriosus: regulation of voltage-gated K+ channels in smooth muscle cells by a mitochondrial redox sensor. Circ Res 91: 478–486, 2002.Crossref | PubMed | ISI | Google Scholar18 Nakanishi T, Gu H, Hagiwara N, Momma K. Mechanisms of oxygen-induced contraction of ductus arteriosus isolated from the fetal rabbit. Circ Res 72: 1218–1228, 1993.Crossref | PubMed | ISI | Google Scholar19 Rogers LJ, Deng C. Corticosterone treatment of the chick embryo affects light-stimulated development of the thalamofugal visual pathway. Behav Brain Res 159: 63–71, 2005.Crossref | PubMed | ISI | Google Scholar20 Seidner SR, Chen YQ, Oprysko PR, Mauray F, Tse MM, Lin E, Koch C, Clyman RI. Combined prostaglandin and nitric oxide inhibition produces anatomic remodeling and closure of the ductus arteriosus in the premature newborn baboon. Pediatr Res 50: 365–373, 2001.Crossref | PubMed | ISI | Google Scholar21 Thebaud B, Ladha F, Michelakis ED, Sawicka M, Thurston G, Eaton F, Hashimoto K, Harry G, Haromy A, Korbutt G, Archer SL. Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in alveolarization. Circulation 112: 2477–2486, 2005.Crossref | PubMed | ISI | Google Scholar22 Thebaud B, Michelakis ED, Wu XC, Moudgil R, Kuzyk M, Dyck JR, Harry G, Hashimoto K, Haromy A, Rebeyka I, Archer SL. Oxygen-sensitive Kv channel gene transfer confers oxygen responsiveness to preterm rabbit and remodeled human ductus arteriosus: implications for infants with patent ductus arteriosus. Circulation 110: 1372–1379, 2004.Crossref | PubMed | ISI | Google Scholar23 Tristani-Firouzi M, Reeve HL, Tolarova S, Weir EK, Archer SL. Oxygen-induced constriction of rabbit ductus arteriosus occurs via inhibition of a 4-aminopyridine-, voltage-sensitive potassium channel. J Clin Invest 98: 1959–1965, 1996.Crossref | PubMed | ISI | Google Scholar24 Villamor E, Kessels CG, Ruijtenbeek K, van Suylen RJ, Belik J, de Mey JG, Blanco CE. Chronic in ovo hypoxia decreases pulmonary arterial contractile reactivity and induces biventricular cardiac enlargement in the chicken embryo. Am J Physiol Regul Integr Comp Physiol 287: R642–R651, 2004.Link | ISI | Google Scholar25 Weir EK, Lopez-Barneo J, Buckler KJ, Archer SL. Acute oxygen-sensing mechanisms. N Engl J Med 353: 2042–2055, 2005.Crossref | PubMed | ISI | Google Scholar26 Williams ML, Coleman JE, Haire SE, Aleman TS, Cideciyan AV, Sokal I, Palczewski K, Jacobson SG, Semple-Rowland SL. Lentiviral expression of retinal guanylate cyclase-1 (RetGC1) restores vision in an avian model of childhood blindness. PLoS Med 3: e201, 2006.Crossref | PubMed | ISI | Google Scholar27 Zhu L, Dagher E, Johnson DJ, Bedell-Hogan D, Keeley FW, Kagan HM, Rabinovitch M. A developmentally regulated program restricting insolubilization of elastin and formation of laminae in the fetal lamb ductus arteriosus. Lab Invest 68: 321–331, 1993.PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: E. Michelakis, Pulmonary Hypertension Program, Dept. of Medicine (Cardiology), Univ. of Alberta, WMC 2C2.36, 8440 112th St., Edmonton, AB, CANADA, T6G 2B7 (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Cited ByReactive oxygen species as mediators of oxygen signaling during fetal-to-neonatal circulatory transitionFree Radical Biology and Medicine, Vol. 142Effect of taurine and gold nanoparticles on the morphological and molecular characteristics of muscle development during chicken embryogenesisArchives of Animal Nutrition, Vol. 66, No. 1Developmental changes in mesenteric artery reactivity in embryonic and newly hatched chicks28 May 2011 | Journal of Comparative Physiology B, Vol. 181, No. 8Vasoactivity of the gasotransmitters hydrogen sulfide and carbon monoxide in the chicken ductus arteriosusSaskia van der Sterren, Pamela Kleikers, Luc J. I. Zimmermann, and Eduardo Villamor1 October 2011 | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 301, No. 4Endothelium-dependent contraction induced by acetylcholine in the chicken ductus arteriosus involves cyclooxygenase-1 activation and TP receptor stimulationComparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, Vol. 157, No. 1Hypoxia sensing in the fetal chicken femoral artery is mediated by the mitochondrial electron transport chainBea Zoer, Angel L. Cogolludo, Francisco Perez-Vizcaino, Jo G. R. De Mey, Carlos E. Blanco, and Eduardo Villamor1 April 2010 | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 298, No. 4Maturation of O2 sensing and signaling in the chicken ductus arteriosusAngel L. Cogolludo, Javier Moral-Sanz, Saskia van der Sterren, Giovanna Frazziano, Anne N. H. van Cleef, Carmen Menéndez, Bea Zoer, Enrique Moreno, Angela Roman, Francisco Pérez-Vizcaino, and Eduardo Villamor1 October 2009 | American Journal of Physiology-Lung Cellular and Molecular Physiology, Vol. 297, No. 4Morphological and Functional Alterations of the Ductus Arteriosus in a Chicken Model of Hypoxia-Induced Fetal Growth RetardationPediatric Research, Vol. 65, No. 3Developmental changes in the effects of prostaglandin E2 in the chicken ductus arteriosus26 August 2008 | Journal of Comparative Physiology B, Vol. 179, No. 2Prenatal Development of Cardiovascular Regulation in Avian Species12 June 2009Effects of hypoxic and hyperoxic incubation on the reactivity of the chicken embryo ( Gallus gallus ) ductus arteriosi in response to catecholamines and oxygen22 December 2008 | Experimental Physiology, Vol. 94, No. 1Mechanisms mediating the oxygen-induced vasoreactivity of the ductus arteriosus in the chicken embryoHenry Greyner, and Edward M. Dzialowski1 November 2008 | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 295, No. 5Maturation of the contractile response of the Emu ductus arteriosus11 December 2007 | Journal of Comparative Physiology B, Vol. 178, No. 3 More from this issue > Volume 292Issue 1January 2007Pages R481-R484 Copyright & PermissionsCopyright © 2007 the American Physiological Societyhttps://doi.org/10.1152/ajpregu.00654.2006PubMed16990484History Received 15 September 2006 Accepted 15 September 2006 Published online 1 January 2007 Published in print 1 January 2007 Metrics
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