Skip to main content
SpringerLink
Log in

Pulmonary Vascular Remodeling in Hypoxic Pulmonary Hypertension

  • Chapter
Hypoxic Pulmonary Vasoconstriction

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 252))

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Allen K and Haworth SG. Impaired adaptation of intrapulmonary arteries to intrauterine life in the newborn pig exposed to hypoxia: an ultrastructural study. Fed. Proc. 1986; 45:879a.

    Google Scholar 

  2. Ambalavanan N, Philips JB, 3rd, Bulger A, Oparil S, and Chen YF. Endothelin-A receptor blockade in porcine pulmonary hypertension. Pediatr. Res. 2002; 52:913–921.

    Article  CAS  PubMed  Google Scholar 

  3. Arrigoni FI, Vallance P, Haworth SG, and Leiper JM. Metabolism of asymmetric dimethylarginines is regulated in the lung developmentally and with pulmonary hypertension induced by hypobaric hypoxia. Circulation 2003; 107:1195–1201.

    Article  CAS  PubMed  Google Scholar 

  4. Balasubramaniam V, Tang JR, Maxey A, Plopper CG, and Abman SH. Mild hypoxia impairs alveolarization in the endothelial nitric oxide synthase-deficient mouse. Am. J. Physiol. Lung Cell. Mol. Physiol. 2003; 284:L964–971.

    CAS  PubMed  Google Scholar 

  5. Belik J, Keeley FW, Baldwin F, and Rabinovitch M. Pulmonary hypertension and vascular remodeling in fetal sheep. Am. J. Physiol. 1994; 266:H2303–H2309.

    CAS  PubMed  Google Scholar 

  6. Berkenbosch JW, Baribeau J, and Perrault T. Decreased synthesis and vasodilation to nitric oxide in piglets with hypoxia-induced pulmonary hypertension. Am. J. Physiol. Lung Cell. Mol. Physiol. 2000; 278: L276–L283.

    CAS  PubMed  Google Scholar 

  7. Brusselmans K, Compernolle V, Tjwa M, Wiesener MS, Maxwell PH, Collen D, and Carmeliet P. Heterozygous deficiency of hypoxia-inducible factor-2alpha protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia. J. Clin. Invest. 2003; 111: 1519–1527.

    Article  CAS  PubMed  Google Scholar 

  8. Champion HC, Bivalacqua TJ, Toyoda K, Heistad DD, Hyman AL, and Kadowitz PJ. In vivo gene transfer ofprepro-calcitonin gene-related peptide to the lung attenuates chronic hypoxia-induced pulmonary hypertension in the mouse. Circulation 1000; 101:923–930.

    Google Scholar 

  9. Chassagne C, Eddahibi S, Adamy C, Rideau D, Marotte F, Dubois-Rande JL, Adnot S, Samuel JL, and Teiger E. Modulation of angiotensin II receptor expression during development and regression of hypoxic pulmonary hypertension. Am. J. Respir. Cell Mol. Biol. 2000; 22:323–332.

    CAS  PubMed  Google Scholar 

  10. Cohen AH, Hanson K, Morris K, Fouty B, McMurty IF, Clarke W, and Rodman DM. Inhibition of cyclic 3′-5′-guanosine monophosphate-specific phosphodiesterase selectively vasodilates the pulmonary circulation in chronically hypoxic rats. J. Clin. Invest. 1996; 97:172–179,.

    CAS  PubMed  Google Scholar 

  11. Das M, Dempsey EC, Bouchey D, Reyland ME, and Stenmark KR. Chronic hypoxia induces exaggerated growth responses in pulmonary artery adventitial fibroblasts: Potential contribution of specific protein kinase c isozymes. Am. J. Respir. Cell Mol. Biol. 2000; 22; 15–25.

    CAS  PubMed  Google Scholar 

  12. Davie NJ, Crossno JT, Frid MG, Hofmeister SE, Reeves JT, Hyde DM, Carpenter TC, Brunetti JA, McNiece IK, and Stenmark KR. Hypoxia-induced pulmonary artery adventitial remodeling and neovascularization: potential contribution of circulating progenitor cells (R1). Am. J. Physiol. Lung. Cell. Mol. Physiol. 2003 (in press).

    Google Scholar 

  13. Davies G and Reid L. Effect of scoliosis on growth of alveoli and pulmonary arteries and on right ventricle. Arch. Dis. Child. 1971; 46:623–632.

    CAS  PubMed  Google Scholar 

  14. Dempsey EC, Stenmark KR, McMurtry IF, O’Brien RF, Voelkel NF, and Badesch DB. Insulin-like growth factor I and protein kinase C activation stimulate pulmonary artery smooth muscle cell proliferation through separate but synergistic pathways. J. Cell. Physiol. 1990; 144: 159–165.

    Article  CAS  PubMed  Google Scholar 

  15. Eddahibi S, Humbert M, Fadel E, Raffestin B, Darmon M, Capron F, Simmoneau G, Dartevelle P, Hamon M, and Adnot S. Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension. J. Clin. Invest. 2001; 108: 1141–1150.

    Article  CAS  PubMed  Google Scholar 

  16. Garg HG, Thompson BT, and Hales CA. Structural determinants of antiprolifer ative activity of heparin on pulmonary artery smooth muscle cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 2000; 279: L779–789.

    CAS  PubMed  Google Scholar 

  17. Grover RF, Vogel JH, Voigt GC, and Blount SGJ. Reversal of high altitude pulmonary hypertension. Am. J. Cardiol. 1966; 18: 928–932.

    Article  CAS  PubMed  Google Scholar 

  18. Hoshikawa Y, Nana-Sinkam P, Moore MD, Sotto-Santiago S, Phang T, Keith RL, Morris KG, Kondo T, Tuder RM, Voelkel NF, and Geraci MW. Hypoxia induces different genes in the lungs of rats compared with mice. Physiol. Genomics 2003; 12: 209–219.

    CAS  PubMed  Google Scholar 

  19. Keegan A, Morecroft I, Smillie D, Hicks MN, and MacLean MR. Contribution of the 5-HTIB receptor to hypoxia-induced pulmonary hypertension: converging evidence using 5-HTIB− receptor knockout mice and the 5-HTIB/ID-receptor antagonist GR 127935. Circ. Res. 2001; 89: 1231–1239.

    CAS  PubMed  Google Scholar 

  20. Kobayashi J and Rabinovitch M. Elastin-bound serum factor and endothelial cell factor induce pulmolnary artery smooth muscle cell elastolytic activity. Circulation 1994; 90(4, part II): I-417.

    Google Scholar 

  21. Kobayashi J, Wigle D, Childs T, Zhu L, Keeley FW, and Rabinovitch M. Serum-induced vascular smooth muscle cell elastolytic activity through tyrosine kinase intracellular signalling. J. Cell. Physiol. 1994; 160: 121–131.

    Article  CAS  PubMed  Google Scholar 

  22. Kouyoumdjian C, Adnot S, Levame M, Eddahibi S, Bousbaa H, and Raffestin B. Continuous inhalation of nitric oxide protects against development of pulmonary hypertension in chronically hypoxic rats. J. Clin. Invest. 1994; 94: 578–584.

    CAS  PubMed  Google Scholar 

  23. Launay JM, Herve P, Peoc’h K, Tournois C, Callebert J, Nebigil CG, Etienne N, Drouet L, Humbert M, Simonneau G, and Maroteaux L. Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension. Nat. Med. 2002; 8: 1129–1135.

    Article  CAS  PubMed  Google Scholar 

  24. Le Cras TD, Markham NE, Tuder RM, Voelkel NF, and Abman SH. Treatment of newborn rats with a VEGF receptor inhibitor causes pulmonary hypertension and abnormal lung structure. Am. J. Physiol. Lung Cell. Mol Physiol. 2002; 283: L555–562.

    PubMed  Google Scholar 

  25. Liu JM and Davidson JM. The elastogenic effect of recombinant transforming growth factor-beta on porcine aortic smooth muscle cells. Biochem. Biophys. Res. Commun. 1988; 154:895–901.

    CAS  PubMed  Google Scholar 

  26. Louzier V, Raffestin B, Leroux A, Branellec D, Caillaud JM, Levame M, Eddahibi S, and Adnot S. Role of VEGF-B in the lung during development of chronic hypoxic pulmonary hypertension. Am. J. Physiol. Lung Cell. Mol. Physiol. 2003; 284: L926–937.

    CAS  PubMed  Google Scholar 

  27. Madden MC, Vender RL, and Friedman M. Effect of hypoxia on prostacyclin production in cultured pulmonary artery endothelium. Prostaglandins 1986; 31: 1049–1062.

    Article  CAS  PubMed  Google Scholar 

  28. Maruyama K, Ye CL, Woo M, Venkatacharya H, Lines LD, Silver MM, and Rabinovitch M. Chronic hypoxic pulmonary hypertension in rats and increased elastolytic activity. Am. J. Physiol. 1991; 261: H1716–1726.

    CAS  PubMed  Google Scholar 

  29. McMurtry IF, Frith CH, and Will DH. Cardiopulmonary responses of male and female swine to simulated high altitude. J. Appl. Physiol. 1973; 35: 459–462.

    CAS  PubMed  Google Scholar 

  30. Meyrick B and Reid L. Endothelial and subintimal changes in rat hilar pulmonary artery during recovery from hypoxia. Lab. Invest. 1980; 42: 603–615.

    CAS  PubMed  Google Scholar 

  31. Minamino T, Christou H, Hsieh CM, Liu Y, Dhawan V, Abraham NG, Perrella MA, Mitsialis SA, and Kourembanas S. Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia. Proc. Natl. Acad. Sci. U.S.A. 2001; 98: 8798–8803.

    Article  CAS  PubMed  Google Scholar 

  32. Mitani Y, Zaidi SHE, Dufourcq P, Thompson K, and Rabinovitch M. Nitric oxide reduces vascular smooth muscle cell elastase activity through cGMP-mediated suppression of ERK phosphorylation and AML1B nuclear partitioning. FASEB J. 2000; 14: 805–814.

    CAS  PubMed  Google Scholar 

  33. Morrell NW, Morris KG, and Stenmark KR. Role of angiotensin converting enzyme and angiotensin II in the development of hypoxic pulmonary hypertension. Am. J. Physiol. 1995; 269: H1186–H1194.

    CAS  PubMed  Google Scholar 

  34. Poiani GJ, Tozzi CA, Choe JK, Yohn SE, and Riley DJ. An antifibrotic agent reduces blood pressure in established pulmonary hypertension in the rat. J. Appl. Physiol. 1990; 68: 1542–1546.

    CAS  PubMed  Google Scholar 

  35. Pozeg ZI, Michelakis ED, McMurtry MS, Thebaud B, Wu XC, Dyck JR, Hashimoto K, Wang S, Moudgil R, Harry G, Sultanian R, Koshal A, and Archer SL. In vivo gene transfer of the O2-sensitive potassium channel Kv1.5 reduces pulmonary hypertension and restores hypoxic pulmonary vasoconstriction in chronically hypoxic rats. Circulation 2003; 107: 2037–2044.

    Article  CAS  PubMed  Google Scholar 

  36. Prosser IW, Stenmark KR, Suthar M, Crouch EC, Mecham RP, and Parks WC. Regional heterogeneity of elastin and collagen gene expression in intralobar arteries in response to hypoxic pulmonary hypertension as demonstrated by in situ hybridization. Am. J. Pathol. 1989; 135: 1073–1088.

    CAS  PubMed  Google Scholar 

  37. Quinn DA, Dahlberg CG, Bonventre JP, Scheid CR, Honeyman T, Joseph PM, Thompson BT, and Hales CA. The role of Na+/H+ exchange and growth factors in pulmonary artery smooth muscle cell proliferation. Am. J. Respir. Cell Mol. Biol. 1996; 14: 139–145.

    CAS  PubMed  Google Scholar 

  38. Rabinovitch M, Boudreau N, Vella G, Coceani F, and Olley PM. Oxygen-related prostaglandin synthesis in ductus arteriosus and other vascular cells. Pediatr. Res. 1989; 26: 330–335.

    CAS  PubMed  Google Scholar 

  39. Rabinovitch M, Gamble WJ, Miettinen OS, and Reid L. Age and sex influence on pulmonary hypertension of chronic hypoxia on recovery. Am. J. Physiol. 1981; 240: H62–H72.

    CAS  PubMed  Google Scholar 

  40. Rabinovitch M, Mullen M, Rosenberg H, Maruyama K, O’Brodovich H, and Olley P. Angiotensin II prevents hypoxic pulmonary hypertension and vascular changes in rats. Am. J. Physiol. 1988; 254: H500–H508.

    CAS  PubMed  Google Scholar 

  41. Ryland D and Reid L. The pulmonary circulation in cystic fibrosis. Thorax 1975; 30: 285–308.

    CAS  PubMed  Google Scholar 

  42. Sato K, Rodman DM, and McMurtry IF. Hypoxia inhibits increased ETB receptor-mediated NO synthesis in hypertensive rat lungs. Am. J. Physiol. 1999; 276: L571–581.

    CAS  PubMed  Google Scholar 

  43. Stenmark KR, Fasules J, Hyde DM, Voelkel NF, Henson J, Tucker A, Wilson H, and Reeves JT. Severe pulmonary hypertension and arterial adventitial changes in newborn calves at 4,300 m. J. Appl. Physiol. 1987; 62: 821–830.

    CAS  PubMed  Google Scholar 

  44. Taraseviciene-Stewart L, Gera L, Hirth P, Voelkel NF, Tuder RM, and Stewart JM. A bradykinin antagonist and a caspase inhibitor prevent severe pulmonary hypertension in a rat model. Can. J. Physiol. Pharmacol. 2002; 80: 269–274.

    Article  CAS  PubMed  Google Scholar 

  45. Thompson BT, Spence CR, Janssens SP, Joseph PM, and Hales CA. Inhibition of hypoxic pulmonary hypertension by heparins of differing in vitro antiproliferative potency. Am. J. Respir. Crit. Care. Med. 1994; 149: 1512–1517.

    CAS  PubMed  Google Scholar 

  46. Thompson K, Kobayashi J, Childs T, Wigle D, and Rabinovitch M. Endothelial and serum factors which include apolipoprotein A1 tether elastin to smooth muscle cells inducing serine elastase activity via tyrosine kinase-mediated transcription and translation. J. Cell Physiol. 1998; 174: 78–89.

    Article  CAS  PubMed  Google Scholar 

  47. Thompson K and Rabinovitch M. Exogenous leukocyte and endogenous elastases can mediate mitogenic activity in pulmonary artery smooth muscle cells by release of extracellular-matrix bound basic fibroblast growth factor. J. Cell Physiol. 1996; 166: 495–505.

    CAS  PubMed  Google Scholar 

  48. Tozzi CA, Wilson FJ, Yu SY, and Riley DJ. Vascular connective tissue is rapidly degraded during early regression of pulmonary hypertension. Chest 1991; 99: 41S–42S.

    CAS  PubMed  Google Scholar 

  49. Tucker A, McMurtry IF, Reeves JT, Alexander AF, Will DH, and Grover RF. Lung vascular smooth muscle as a determinant of pulmonary hypertension at high altitude. Am. J. Physiol. 1975; 228: 762–767.

    CAS  PubMed  Google Scholar 

  50. Vieillard-Baron A, Frisdal E, Eddahibi S, Deprez I, Baker AH, Newby AC, Berger P, Levame M, Raffestin B, Adnot S, and ďOrtho MP. Inhibition of matrix metalloproteinases by lung TIMP-1 gene transfer or doxycycline aggravates pulmonary hypertension in rats. Circ. Res. 2000; 87: 418–425.

    CAS  PubMed  Google Scholar 

  51. Voelkel NF, Tuder RM, Wade K, Hoper M, Lepley RA, Goulet JL, Koller BH, and Fitzpatrick F. Inhibition of 5-lipoxygenase-activating protein (FLAP) reduces pulmonary vascular reactivity and pulmonary hypertension in hypoxic rats. J. Clin. Invest. 1996; 97: 2491–2498.

    CAS  PubMed  Google Scholar 

  52. Wanstall JC, Gambino A, Jeffery TK, Cahill MM, Bellomo D, Hayward NK, and Kay GF. Vascular endothelial growth factor-B-deficient mice show impaired development of hypoxic pulmonary hypertension. Cardiovasc. Res. 2002; 55: 361–368.

    Article  CAS  PubMed  Google Scholar 

  53. Wigle DA, Thompson KE, Yablonsky S, Zaidi SHE, Coulber C, Jones PL, and Rabinovitch M. AML1-like transcription factor induces serine elastase activity in ovine pulmonary artery smooth muscle cells. Circ. Res. 1998; 83(3):252–263.

    CAS  PubMed  Google Scholar 

  54. Yet SF, Perrella MA, Layne MD, Hsieh CM, Maemura K, Kobzik L, Wiesel P, Christou H, Kourembanas S, and Lee ME. Hypoxia induces severe right ventricular dilatation and infarction in heme oxygenase-1 null mice. J. Clin. Invest. 1999; 103: R23–R29.

    CAS  PubMed  Google Scholar 

  55. Yu A, Shimoda LA, Iyer NV, Huso DL, Sun X, McWilliams R, Beaty T, Sham JS, Wiener CM, and Sylvester JT. Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor-1-alpha. J. Clin. Invest. 1999; 103: 691–696.

    CAS  PubMed  Google Scholar 

  56. Zaidi SHE, You X-M, Ciura S, Husain M, and Rabinovitch M. Overexpression of the serine elastase inhibitor elafin protects transgenic mice from hypoxic pulmonary hypertension. Circulation 2002; 105: 516–521.

    Article  CAS  PubMed  Google Scholar 

  57. Zhao L, Mason NA, Strange JW, Walker H, and Wilkins MR. Beneficial effects of phosphodiesterase 5 inhibition in pulmonary hypertension are influenced by natriuretic Peptide activity. Circulation 2003; 107: 234–237.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Stanford University School of Medicine, Stanford, California, USA

    Marlene Rabinovitch

Authors
  1. Marlene Rabinovitch
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Medicine, University of California, San Diego School of Medicine, San Diego, California

    Jason X. -J. Yuan M.D., Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Kluwer Academic Publishers

About this chapter

Cite this chapter

Rabinovitch, M. (2004). Pulmonary Vascular Remodeling in Hypoxic Pulmonary Hypertension. In: Yuan, J.X.J. (eds) Hypoxic Pulmonary Vasoconstriction. Developments in Cardiovascular Medicine, vol 252. Springer, Boston, MA. https://doi.org/10.1007/1-4020-7858-7_23

Download citation

  • DOI: https://doi.org/10.1007/1-4020-7858-7_23

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4020-7857-6

  • Online ISBN: 978-1-4020-7858-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation