Abstract
Within minutes after birth, pulmonary vascular resistance (PVR) rapidly falls from high fetal levels. This allows pulmonary blood flow to increase nearly tenfold and enables the lung to assume its postnatal role in gas exchange. Failure of the pulmonary circulation to successfully achieve and sustain this decrease in PVR causes severe hypoxemia in many neonatal cardiopulmonary disorders, which are referred to as the syndrome persistent pulmonary hypertension of the newborn (PPHN). Mechanisms leading to severe pulmonary hypertension after birth are poorly understood, but they include altered pulmonary vascular reactivity and structure. Persistent pulmonary hypertension of the newborn is a major clinical problem, contributing substantially to morbidity and mortality in both full-term and premature neonates. An understanding of basic mechanisms that underlie normal development of the pulmonary circulation in utero and that contribute to the marked pulmonary vasodilation during the normal transition at birth may provide insight into PPHN and related disorders.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Abman, S.H. and F.J. Accurso. Acute effects of partial compression of the ductus arteriosus on the fetal pulmonary circulation. Am. J. Physiol. 257: H626–634, 1989.
Abman, S.H. and F.J. Accurso. Sustained fetal pulmonary vasodilation during prolonged infusion of atrial natriuretic factor and 8-bromo-guanosine monophosphate. Am. J. Physiol. 260: H183–H192, 1991.
Abman, S.H., B.A. Chatfield, S.L. Hall, and I.F. McMurtry. Role of endothelium-derived relaxing factor during transition of pulmonary circulation at birth. Am. J. Physiol. 259: H1921–H1927, 1990.
Abman, S.H., B.A. Chatfield, D.M. Rodman, S.L. Hall, and I.F. McMurtry. Maturation-related changes in endothelium-dependent relaxation of ovine pulmonary arteries. Am. J. Physiol. 260: L280–L285, 1991.
Abman, S.H., J.P. Kinsella, M.S. Schaffer, and R.B. Wilkening. Inhaled nitric oxide therapy in a premature newborn with severe respiratory distress and pulmonary hypertension. Pediatrics 92: 606–609, 1993.
Abman, S.H., P.F. Shanley, and F.J. Accurso. Failure of postnatal adaptation of the pulmonary circulation after chronic intrauterine pulmonary hypertension in fetal lambs. J. Clin. Invest. 83: 1849–1858, 1989.
Accurso, F.J., B. Alpert, R.B. Wilkening, R.G. Petersen, and G. Meschia. Time-dependent response of fetal pulmonary blood flow to an increase in fetal oxygen tension. Respir. Physiol. 63: 43–52, 1986.
Allen, K. and S.G. Haworth. Impaired adaptation of intrapulmonary arteries to extrauterine life in newborn pigs exposed to hypoxia. An ultrastructural study. Fed. Proc. 45: 879, 1986.
Allen, S.W., B.A. Chatfield, S.L. Koppenhafer, M.S. Schaffer, R.R. Wolfe, and S.H. Abman. Circulating immunoreactive ET-1 in children with pulmonary hypertension: association with acute hypoxic pulmonary vasoreactivity. Am. Rev. Respir. Dis. 148: 519–522, 1993.
Archer, S.L., J.M.C. Huang, V. Hampl, D.F. Nelson, P.J. Shultz, and E.K. Weir. NO and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc. Natl. Acad. Sci. USA 91: 7583–7587, 1994.
Arnal, J.F., J. Yamin, S. Dockery, and D.G. Harrison. Regulation of endothelial NO synthase mRNA, protein, and activity during cell growth. Am. J. Physiol. 267: C1381–C1388, 1994.
Beavo, J.A. and D.H. Reifsnyder. Primary sequence of cyclic nucleotide phosphodiesterase isozymes and the design of selective inhibitors. Trends Pharmacol. Sci. 11: 150–155, 1990.
Belik, J. and N.L. Stephens. Developmental differences in vascular smooth muscle mechanics in pulmonary and systemic circulations. J. Appl. Physiol. 74: 682–687, 1993.
Bolotina, V.M., S. Najibi, J.J. Palacino, P.H. Pagano, and R.A. Cohen. NO directly activates calcium-dependent potassium channels in vascular smooth muscle. Nature 368: 850–853, 1994.
Bonvallet, S.T., M.A. Zamora, K. Hasunuma, K. Sato, N. Hanasato, D. Anderson, K. Sato, and T.J. Stelzner. BQ123, an ETA-receptor antagonist, attenuates hypoxic pulmonary hypertension in rats. Am. J. Physiol. 266: H1327–H331, 1994.
Boulanger, C. and T.F. Luscher. Release of endothelin from the porcine aorta. Inhibition by endothelium-derived nitric oxide. J. Clin. Invest. 85: 87–90, 1990.
Bustamante, S.A., Y. Pang, S. Romero, M.R. Pierce, C.A. Voelker, J.H. Thompson, M. Sandoval, X. Liu, and M.J. Miller. Inducible NOS and the regulation of central vessel caliber in the fetal rat. Circulation 1948–1953, 1996.
Braner, D.A., J.R. Fineman, R. Chang, and S.J. Soifer. MandB 22948, a cGMP phosphodiesterase inhibitor, is a pulmonary vasodilator in lambs. Am. J. Physiol. 764: H252–H258, 1993.
Cassin, S. Role of prostaglandins, thromboxanes and leukotrienes in the control of the pulmonary circulation in the fetus and newborn. Semin. Perinatol. 11: 53–63, 1987.
Cassin, S., G.S. Dawes, J.C. Mott, B.B. Ross, and L.B. Strang. Vascular resistance of the foetal and newly ventilated lung of the lamb. J. Physiol. Lond. 171: 61–79, 1964.
Cassin, S., T. Kristova, T. Davis, P. Kadowitz, and G. Gause. Tone-dependent responses to endothelin in the isolated perfused fetal sheep pulmonary circulation in situ. J. Appl. Physiol. 70: 1228–1234, 1991.
Chatfield, B.A., I.F. McMurtry, S.L. Hall, and S.H. Abman. Hemodynamic effects of endothelin-1 on the ovine fetal pulmonary circulation. Am. J. Physiol. 261: R182–R187, 1991.
Cohen, A.H., K. Hanson, K. Morris, B. Fouty, I.F. McMurtry, W. Clarke, and D.M. Rodman. Inhibition of cGMP-specific phosphodiesterase selectively vasodilates the pulmonary circulation in chronically hypoxic rats. J. Clin. Invest. 97: 172–179, 1996.
Cornfield, D.N., B.A. Chatfield, J.A. McQueston, I.F. McMurtry, and S.H. Abman. Effects of birth-related stimuli on L-arginine-dependent pulmonary vasodilation in the ovine fetus. Am. J. Physiol. 262: H1474–H1481, 1992.
Cornfield, D.N., J.A. McQueston, I.F. McMurtry, D.M. Rodman, and S.H. Abman. Role of ATPsensitive K+channels in ovine fetal pulmonary vascular tone. Am. J. Physiol. 263: H1363–H1368, 1992.
Cornfield, D.N., H.L. Reeves, S. Tolarova, E.K. Weir, and S.L. Archer. Oxygen causes fetal pulmonary vasodilation through activation of a calcium-dependent potassium channel. Proc. Natl. Acad. Sci. USA 93: 8089–8094, 1996.
Davidson, D. and A. Eldemerdash. Endothelium-derived relaxing factor: evidence that it regulates pulmonary vascular resistance in the isolated newborn guinea pig lung. Pediatr. Res. 29: 538–542, 1991.
Dubin, D., R.E. Pratt, J.P. Cooke, and V.J. Dzau. Endothelin, a potent vasoconstrictor, is a vascular smooth muscle mitogen. J. Vasc. Med. Biol. 1: 150–154, 1989.
Fineman, J.R., J. Wong, F.C. Morin, L.M. Wild, and S.J. Soifer. Chronic NO inhibition in utero produces persistent pulmonary hypertension in newborn lambs. J. Clin. Invest. 93: 9675–9683, 1994.
Flowers, M.A., Y. Wang, R.J. Stewart, B. Patel, and P.A. Marsden. Reciprocal regulation of endothelin-1 and endothelial NOS in proliferating endothelial cells. Am. J. Physiol. 269: H1988–H1997, 1995.
Fratacci, M.D., C.G. Frostell, T.Y. Chen, and W.M. Zapol. Inhaled NO: a selective pulmonary vasodilator of heparin-protamine vasoconstriction in sheep. Anesthesiology 75: 990–999, 1991.
Garg, U.C. and A. Hassid. NO-generating vasodilators and 8-bromo-cGMP inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle ceils. J. Clin. Invest. 83: 1774–1777, 1989.
Geggel, R.L. and L.M. Reid. The structural basis of persistent pulmonary hypertension of the newborn. Clin. Perinatol. 3: 525–549, 1984.
Giaid, A. and D. Saleh. Reduced expression of endothelial NO synthase in the lungs of patients with pulmonary hypertension. N. Engl. J. Med. 333: 214–221, 1995.
Giaid, A., M. Yanagasawa, D. Langleben, R.P. Michel, R. Levy, H. Shennib, S. Kimura, T. Masaki, W.P. Duguid, and D.J. Stewart. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N. Engl. J. Med. 328: 1732–1739, 1993.
Goldberg, S.J., R.A. Levy, and B. Siassi. Effects of maternal hypoxia and hyperoxia upon the neonatal pulmonary vasculature. Pediatrics 48: 528–533, 1971.
Halbower, A.C., R.M. Tuder, W.A. Franklin, J.S. Pollock, U. Forstermann, and S.H. Abman. Maturation-related changes in endothelial NO synthase immunolocalization in the developing ovine lung. Am. J. Physiol. 267: L585–L591, 1994.
Hanson, K.A., J.A. Beavo, S.H. Abman, and W.R. Clarke. Chronic intrauterine pulmonary hypertension increases lung cGMP hydrolytic activity and decreases cGMP kinase content in the ovine fetus [Abstract]. Am. J. Respir. Crit. Care Med. 155: A632, 1997.
Hanson, K.A., S. Uezono, J. Beavo, and W.R. Clarke. Developmental regulation of pulmonary cGMP phosphodiesterase activity in fetal and maternal lung [Abstract]. Am. J. Respir. Crit. Care Med. 151: A437, 1995.
Heymann, M.A. and S.J. Soifer. Control of fetal and neonatal pulmonary circulation. In: Pulmonary vascular physiology and pathophysiology, edited by E.K. Weir and J.T. Reeves. New York: Marcel Dekker, 1989, p. 33–50.
Hirata, Y., Y.H. Yoshima, S. Eguchi, K. Kanno, T. Imai, K. Ohta, and F. Marumo. ET receptor subtype B mediates synthesis of NO by cultures bovine endothelial cells. J. Clin. Invest. 91: 1367–1373, 1993.
Hobbs, A.J. and L.J. Ignarro. NO-cGMP signal transduction system. In: Nitric Oxide and the Lung, edited by W.M. Zapol and K. Bloch, New York: Marcel Dekker, 1996, p. 1–57.
Isozaki-Fukuda, Y., T. Kojima, Y. Hirata, N. Ono, S. Sawaragi, I. Sawaragi, and Y. Kobayashi. Plasma immunoreactive ET-1 concentration in human fetal blood: its relation to asphyxia. Pediatr. Res. 30: 244–247, 1991.
Ivy, D.D., J.P. Kinsella, and S.H. Abman. Physiologic characterization of endothelin A and B receptor activity in the ovine fetal pulmonary circulation. J. Clin. Invest. 93: 2141–2148, 1994.
Ivy, D.D., T.A. Parker, J.W. Ziegler, H.L. Galan, J.P. Kinsella, and S.H. Abman. Prolonged endothelin A receptor blockade attenuates chronic intrauterine pulmonary hypertension. J. Clin. Invest. 99: 1179–1186, 1997.
Ivy, D.D., J.W. Ziegler, M.F. Dubus, J.J. Fox, J.P. Kinsella, and S.H. Abman. Chronic intrauterine pulmonary hypertension alters endothelin receptor activity in the ovine fetus. Pediatr. Res. 39: 335–342, 1995.
Ivy, D.D., J.W. Ziegler, J.P. Kinsella, and S.H. Abman. Endothelin blockade augments fetal pulmonary vasodilation. J. Appl. Physiol. 81: 2481–2487, 1996.
Jones, O.W. and S.H. Abman. Systemic and pulmonary hemodynamic effects of big endothelin-1 and phosphoramidon in the ovine fetus. Am. J. Physiol. 266: R929–R935, 1994.
Kinsella, J.P., A.C. Halbower, J.W. Ziegler, J.F. Fox, D.D. Ivy, and S.H. Abman. Effects of inhaled NO on pulmonary edema and lung neutrophil accumulation in severe experimental hyaline membrane disease. Pediatr. Res. 41: 457–463, 1997.
Kinsella, J.P., D.D. Ivy, and S.H. Abman. Inhaled nitric oxide improves gas exchange and lowers pulmonary vascular resistance in severe experimental hyaline membrane disease. Pediatr. Res. 36: 402–408, 1994.
Kinsella, J.P., D.D. Ivy, and S.H. Abman. Ontogeny of NO activity and response to inhaled NO in the developing ovine pulmonary circulation. Am. J. Physiol. 267: H1955–H1961, 1994.
Kinsella, J.P., J.A. McQueston, A.A. Rosenberg, and S.H. Abman. Hemodynamic effects of exogenous nitric oxide in ovine transitional pulmonary circulation. Am. J. Physiol. 263: H875–H880, 1992.
Kinsella, J.P., S.R. Neish, D.D. Ivy, E. Shaffer, and S.H. Abman. Clinical responses to prolonged treatment of persistent pulmonary hypertension of the newborn. J. Pediatr. 123: 103–108, 1993.
Kinsella, J.P., S. Neish, E. Shaffer, and S.H. Abman. Low dose inhalational nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 340: 819–820, 1992.
Kobzik, L., D.S. Bredt, C.J. Lowenstein, J. Drazen, B. Gaston, D. Sugarbaker, and J.S. Stamler. NOS in human and rat lung: immunocytochemical and histochemical localization. Am. J. Respir. Cell Mol. Biol. 9: 371–377, 1993.
Kourembanas, D., L. McQuillan, G. Leung, and D. Faller. NO regulates the expression of vasoconstrictors and growth factors by vascular endothelium under normoxia and hypoxia. J. Clin. Invest. 92: 99–104, 1993.
Kourembanas, S., P.A. Marsden, L.P. McQuillan, and D.V. Faller. Hypoxia induces endothelin gene expression and secretion in cultured human endothelium. J. Clin. Invest. 88: 1054–1057, 1991.
Le Cras, T.D., C. Xue, A. Rengesamy, and R.A. Johns. Chronic hypoxia upregulates endothelial and inducible NO synthase gene and protein expression in rat lung. Am. J. Physiol. 270: L164–L170, 1996.
Leffler, C.W., J.R. Hessler, and R.S. Green. Mechanism of stimulation of pulmonary prostacyclin synthesis at birth. Prostaglandins 28: 877–87, 1984.
Leffler, C.W., T.L. Tyler, and S. Cassin. Effect of indomethacin on pulmonary vascular response to ventilation of fetal goats. Am. J. Physiol. 234: H346–H351, 1978.
Lerman, A., E.K. Sandok, F.L. Hildebrand, and J.C. Burnett. Inhibition of EDRF enhances endothelin-mediated vasoconstriction. Circulation 85: 1894–1898, 1992.
Levin, D.L., M.A. Heymann, J.A. Kitterman, G.A. Gregory, R.H. Phibbs, and A.M. Rudolph. Persistent pulmonary hypertension of the newborn. J. Pediatr. 89: 626–633, 1976.
Levin, D.L., A.I. Hyman, M.A. Heymann, and A.M. Rudolph. Fetal hypertension and the development of increased pulmonary vascular smooth muscle: a possible mechanism for persistent pulmonary hypertension of the newborn infant. J. Pediatr. 92: 265–269, 1978.
Lewis, A.B., M.A. Heymann, and A.M. Rudolph. Gestational changes in pulmonary vascular responses in fetal lambs in utero. Circ. Res. 39: 536–541, 1976.
Li, H., S. Chen, Y. Chen, Q. Meng, J. Durand, S. Oparil, and T. Elton. Enhanced endothelin-1 and endothelin receptor gene expression in chronic hypoxia. J. Appl. Physiol. 77: 1451–1459, 1994.
MacCumber, M.W., C.A. Ross, B.M. Glaser, and S.H. Snyder. Endothelin: visualization of mRNAs by in situ hybridization provides evidence for local action. Proc. Natl. Acad. Sci. USA 86: 7285–7289, 1989.
McQueston, J.A., D.N. Cornfield, I.F. McMurtry, and S.H. Abman. Effects of oxygen and exogenous L-arginine on endothelium-derived relaxing factor activity in the fetal pulmonary circulation. Am. J. Physiol. 264: H865–7871, 1993.
McQueston, J.A., J.P. Kinsella, D.D. Ivy, I.F. McMurtry, and S.H. Abman. Chronic pulmonary hypertension in utero impairs endothelium-dependent vasodilation. Am. J. Physiol. 268: H288–H294, 1995.
McQuillan, L.P., G.K. Leung, P.A. Marsden, S.K. Kostyk, and S. Kourembanas. Hypoxia inhibits expression of eNOS via transcriptional and posttranscriptional mechanisms. Am. J. Physiol. 267: H1921–H1927, 1994.
Michael, J.R. and B.A. Markewitz. Endothelins and the lung. Am. J. Respir. Crit. Care Med. 154: 555–581, 1996.
Moncada, S., R.M.J. Palmer, and E.A. Higgs. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 43: 109–142, 1991.
Morbidelli, L., C.H. Chang, J.G. Douglas, H.J. Granger, C.A. Maggi, P. Geppetti, F. Ledda. NO mediates mitogenic effect of VEGF on coronary venular endothelium. Am. J. Physiol. 270: H411–H415, 1996.
Morin, F.C. Ligating the ductus arteriosus before birth causes persistent pulmonary hypertension in the newborn lamb. Pediatr. Res. 25: 245–250, 1989.
Morin, F.C., E.A. Egan, W. Ferguson, and C.E.G. Lundgren. Development of pulmonary vascular response to oxygen. Am. J. Physiol. 254: H542–H546, 1988.
Neonatal Inhaled NO Study Group. Inhaled NO in full-term and nearly full-term infants with hypoxic respiratory failure. N. Engl. J. Med. 336: 597–604, 1997.
North, A.J., R.A. Star, T.S. Brannon, K. Ujiie, L.B. Wells, C.J. Lowenstien, S.H. Snyder, and P.W. Shaul. NO synthase type I and type III gene expression are developmentally regulated in rat lung. Am. J. Physiol. 266: L635–L641, 1994.
Rairigh, R., T.D. LeCras, D.D. Ivy, J.P. Kinsella, G. Richter, M. Horan, I. Fan, and S.H. Abman. Role of inducible NOS in regulation of pulmonary vascular tone in the ovine fetus. J. Clin Invest 101: 15–21, 1998.
Roberts, J.D., T. Chen, N. Kawai, J. Wain, P. Dupuy, A. Shimouchi, K. Bloch, D. Polaner, and W.M. Zapol. Inhaled NO reverses pulmonary vasoconstriction in the hypoxic and acidoticnewborn lamb. Circ. Res. 72: 246–254, 1993.
Roberts, J.D., J.R. Fineman, F.C. Morin, P.W. Shaul, S. Rimar, M.D. Schreiber, R.A. Polin, M.S. Zwass, M.M. Zayek, I. Gross, M.A. Heymann, and W.M. Zapol. Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. N. Engl. J. Med. 336: 605–610, 1997.
Roberts, J.D., J.P. Kinsella, and S.H. Abman. Inhaled NO in neonatal pulmonary hypertension and severe RDS: experimental and clinical studies. In: Nitric Oxide and the Lung, edited by W.M. Zapol and K. Bloch, New York: Marcel Dekker, 1996, p. 333–363.
Roberts, J.D., D.M. Polaner, P. Lang, and W.M. Zapol. Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 340: 818–819, 1992.
Rossaint, R., K.J. Falcke, F. Lopez, K. Slama, U. Pison, and W.M. Zapol. Inhaled NO for the adult respiratory distress syndrome. N. Engl. J. Med. 328: 399–405, 1993.
Rosenberg, A.A., J. Kennaugh, S.L. Koppenhafer, M. Loomis, and S.H. Abman. Increased immunoreactive endothelin-1 levels in persistent pulmonary hypertension of the newborn. J. Pediatr. 123: 109–114, 1993.
Rudolph, A.M. Fetal and neonatal pulmonary circulation. Annu. Rev. Physiol. 41: 383–395, 1979.
Rudolph A.M., M.A. Heymann, and A.B. Lewis. Physiology and pharmacology of the pulmonary circulation in the fetus and newborn. In: Development of the lung, edited by W. Hodson, New York: Marcel Dekker, 1977, p. 497–453.
Shaul, P.W., E.J. Smart, L.J. Robinson, Z. German, I.S. Yuhanna, Y. Ying, R.G.W. Anderson, and T. Michel. Acylation targets endothelial NO synthase to plasmalemal calveolae. J. Biol. Chem. 271: 6518–6522, 1996.
Shaul, P.W., I.S. Yuhanna, Z. German, Z. Chen, R.H. Steinhorn, and F.C. Morin. Pulmonary endothelial nitric oxide synthase gene expression is decreased in fetal lambs with pulmonary hypertension. Am. J. Physiol. 272: L1005–L1012, 1997.
Soifer, S.J., R.D. Loitz, C. Roman, and M.A. Heymann. Leukotriene end organ antagonists increase pulmonary blood flow infeal lambs. Am. J. Physiol. 249: H570–H576, 1985.
Steinhorn, R.H., J.A. Russell, and F.C. Morin. Pulmonary arteries from newborn lambs with persistent pulmonary hypertension have decreased sensitivity to NO [Abstract]. Pediatr. Res. 35: 354A, 1994.
Stenmark, K.R., S.H. Abman, and F.J. Accurso. Etiologic mechanisms of persistent pulmonary hypertension of the newborn. In: Pulmonary vascular physiology and pathophysiology, edited by E.K. Weir and J.T. Reeves. New York: Marcel Dekker, 1989, p. 335–402.
Stewart, D.J., R.D. Levy, P. Cernacek, and D. Langleben. Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Ann. Intern. Med. 114: 464–469, 1991.
Thébaud, B., P. de Lagausie, E. Souil, Y. Aigrain, J.C. Mercier, and A.T. Dinh-Xuan. Pulmonary vasodilation is not impaired in congenital diaphragmatic hernia [Abstract]. Am. J. Respir. Crit. Care Med. 155: A948, 1997.
Thomae, K.R., D.K. Nakayama, T.R. Billiar, R.L. Simmons, B.R. Pitt, and P. Davies. Effect of NO on fetal pulmonary artery smooth muscle growth. J. Surg. Res. 270: H411–H415, 1996.
Velvis, H., P. Moore, and M.A. Heymann. Prostaglandin inhibition prevents the fall in pulmonary vascular resistance as the result of rhythmic distension of the lungs in fetal lambs. Pediatr. Res. 30: 62–67, 1991.
Villamor, E., T.D. Le Cras, M.P. Horan, A.C. Halbower, R.M. Tuder, and S.H. Abman. Chronic intrauterine hypertension impairs endothelial nitric oxide sythase in the ovine fetus. Am. J. Physiol. 272: L1013–L1020, 1997.
Wang, Y. and F. Coceani. Isolated pulmonary resistance vessels from fetal lambs: contractile behavior and responses to indomethacin and endothelin-1. Circ. Res. 71: 320–330, 1992.
Wallen, L.D., S.F. Perry, J.T. Alston, and J.E. Maloney. Morphometric study of the role of pulmonary arterial flow in fetal lung growth in sheep. Pediatr. Res. 27: 122–127, 1990.
Walther, F.J., F.J. Bender, and J.O. Leighton. Persistent pulmonary hypertension in premature neonates with severe RDS. Pediatrics 90: 899–904, 1992.
Winters, J.W., J. Wong, D. van Dyke, M. Johengen, M.A. Heymann, and J.R. Fineman. Endothelin blockade does not alter the increase in pulmonary blood flow during oxygen ventilation in fetal lambs. Pediatr. Res. 40: 152–157, 1996.
Wong, J., J.R. Fineman, and M.A. Heymann. The role of endothelin and endothelin receptor subtypes in regulation of fetal pulmonary vascular tone. Pediatr. Res. 35: 664–670, 1994.
Yanagisawa, M., H. Kurihara, S. Kirmura, Y. Tomobe, M. Kobayashi, Y. Mitsui, Y. Yazaki, K. Goto, and T. Masaki. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332: 411–415, 1988.
Ziche, M., L. Morbidelli, E. Masini, S. Amerini, H.J. Granger, C.A. Maggi, P. Geppetti, and F. Ledda. NO mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J. Clin. Invest. 94: 2036–2044, 1994.
Ziegler, J.W., D.D. Ivy, J.J. Fox, J.P. Kinsella, W.R. Clarke, and S.H. Abman. Dipyridamole, a cGMP phosphodiesterase inhibitor, causes pulmonary vasodilation in the ovine fetus. Am. J. Physiol. 269: H473–H479, 1995.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 American Physiological Society
About this chapter
Cite this chapter
Abman, S.H., Kinsella, J.P., Mercier, JC. (1999). Nitric Oxide and Endothelin in the Developing Pulmonary Circulation: Physiologic and Clinical Implications. In: Gaultier, C., Bourbon, J.R., Post, M. (eds) Lung Development. Clinical Physiology Series. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7537-8_7
Download citation
DOI: https://doi.org/10.1007/978-1-4614-7537-8_7
Publisher Name: Springer, New York, NY
Online ISBN: 978-1-4614-7537-8
eBook Packages: Springer Book Archive