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Regulation, signalling and functions of hormonal peptides in pulmonary vascular remodelling during hypoxia

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Abstract

Hypoxic state affects organism primarily by decreasing the amount of oxygen reaching the cells and tissues. To adjust with changing environment organism undergoes mechanisms which are necessary for acclimatization to hypoxic stress. Pulmonary vascular remodelling is one such mechanism controlled by hormonal peptides present in blood circulation for acclimatization. Activation of peptides regulates constriction and relaxation of blood vessels of pulmonary and systemic circulation. Thus, understanding of vascular tone maintenance and hypoxic pulmonary vasoconstriction like pathophysiological condition during hypoxia is of prime importance. Endothelin-1 (ET-1), atrial natriuretic peptide (ANP), and renin angiotensin system (RAS) function, their receptor functioning and signalling during hypoxia in different body parts point them as disease markers. In vivo and in vitro studies have helped understanding the mechanism of hormonal peptides for better acclimatization to hypoxic stress and interventions for better management of vascular remodelling in different models like cell, rat, and human is discussed in this review.

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References

  1. J.A. Dempsey, W.G. Reddan, M.L. Birnbaum, H.V. Forster, J.S. Thoden, R.F. Grover, J. Rankin, Effects of acute through life-long hypoxic exposure on exercise pulmonary gas exchange. Respir. Physiol. 13(1), 62–89 (1971)

    Article  CAS  PubMed  Google Scholar 

  2. R. Ashack, M.O. Farber, M.H. Weinberger, G.L. Robertson, N.S. Fineberg, F. Manfredi, Renal and hormonal responses to acute hypoxia in normal individuals. J. Lab. Clin. Med. 106(1), 12–16 (1985)

    CAS  PubMed  Google Scholar 

  3. F.H. Al-Hashem, The effect of high altitude on blood hormones in male Westar rats in South western Saudi Arabia. Am. J. Environ. Sci. 6(3), 268–274 (2010)

    Article  CAS  Google Scholar 

  4. N. Mason, The physiology of high altitude: an introduction to the cardio-respiratory changes occurring on ascent to altitude. Curr. Anaesth. Crit. Care 11(1), 34–41 (2000)

    Article  Google Scholar 

  5. E.R. Swenson, T.B. Duncan, S.V. Goldberg, G. Ramirez, S. Ahmad, R.B. Schoene, Diuretic effect of acute hypoxia in humans: relationship to hypoxic ventilatory responsiveness and renal hormones. J. Appl. Physiol. 78(2), 377–383 (1995)

    Article  CAS  PubMed  Google Scholar 

  6. P. Ariyaratnam, M. Loubani, A.H. Morice, Hypoxic pulmonary vasoconstriction in humans. BioMed. Res. Int. 2013, 623684 (2013). https://doi.org/10.1155/2013/623684

    Article  PubMed  PubMed Central  Google Scholar 

  7. P.I. Aaronson, T.P. Robertson, G.A. Knock, S. Becker, T.H. Lewis, V. Snetkov, J.P. Ward, Hypoxic pulmonary vasoconstriction: mechanisms and controversies. J. Physiol. 570(Pt 1), 53–58 (2006). https://doi.org/10.1113/jphysiol.2005.098855

    Article  CAS  PubMed  Google Scholar 

  8. K.R. Stenmark, K.A. Fagan, M.G. Frid, Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circ. Res. 99(7), 675–691 (2006). https://doi.org/10.1161/01.RES.0000243584.45145.3f

    Article  CAS  PubMed  Google Scholar 

  9. A. Hussain, M.S. Suleiman, S.J. George, M. Loubani, A. Morice, Hypoxic pulmonary vasoconstriction in humans: tale or myth. Open. Cardiovasc. Med. J. 11, 1–13 (2017). https://doi.org/10.2174/1874192401711010001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. A.B. Lumb, P. Slinger, Hypoxic pulmonary vasoconstriction: physiology and anesthetic implications. Anesthesiology 122(4), 932–946 (2015). https://doi.org/10.1097/ALN.0000000000000569

    Article  CAS  PubMed  Google Scholar 

  11. M. Yanagisawa, H. Kurihara, S. Kimura, Y. Tomobe, M. Kobayashi, Y. Mitsui, Y. Yazaki, K. Goto, T. Masaki, A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332(6163), 411–415 (1988). https://doi.org/10.1038/332411a0

    Article  CAS  PubMed  Google Scholar 

  12. D. Xu, N. Emoto, A. Giaid, C. Slaughter, S. Kaw, D. deWit, M. Yanagisawa, ECE-1: a membrane-bound metalloprotease that catalyzes the proteolytic activation of big endothelin-1. Cell 78(3), 473–485 (1994)

    Article  CAS  PubMed  Google Scholar 

  13. T.J. Opgenorth, J.R. Wu-Wong, K. Shiosaki, Endothelin-converting enzymes. FASEB J. 6(9), 2653–2659 (1992)

    Article  CAS  PubMed  Google Scholar 

  14. T. Sakurai, M. Yanagisawa, Y. Takuwa, H. Miyazaki, S. Kimura, K. Goto, T. Masaki, Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. Nature 348(6303), 732–735 (1990). https://doi.org/10.1038/348732a0

    Article  CAS  PubMed  Google Scholar 

  15. V.J. Harrison, R. Corder, E.E. Anggard, J.R. Vane, Evidence for vesicles that transport endothelin-1 in bovine aortic endothelial cells. J. Cardiovasc. Pharmacol. 22(Suppl 8), S57–S60 (1993)

    Article  CAS  PubMed  Google Scholar 

  16. M.J. Boscoe, A.T. Goodwin, M. Amrani, M.H. Yacoub, Endothelins and the lung. Int. J. Biochem. Cell. Biol. 32(1), 41–62 (2000)

    Article  CAS  PubMed  Google Scholar 

  17. Y. Miyoshi, Y. Nakaya, T. Wakatsuki, S. Nakaya, K. Fujino, K. Saito, I. Inoue, Endothelin blocks ATP-sensitive K+ channels and depolarizes smooth muscle cells of porcine coronary artery. Circ. Res. 70(3), 612–616 (1992)

    Article  CAS  PubMed  Google Scholar 

  18. M.J. Kuchan, J.A. Frangos, Shear stress regulates endothelin-1 release via protein kinase C and cGMP in cultured endothelial cells. Am. J. Physiol. 264(1 Pt 2), H150–H156 (1993)

    CAS  PubMed  Google Scholar 

  19. K. Sato, Y. Morio, K.G. Morris, D.M. Rodman, I.F. McMurtry, Mechanism of hypoxic pulmonary vasoconstriction involves ET(A) receptor-mediated inhibition of K(ATP) channel. Am. J. Physiol. Lung Cell. Mol. Physiol. 278(3), L434–L442 (2000)

    Article  CAS  PubMed  Google Scholar 

  20. M.J. Horgan, J.M. Pinheiro, A.B. Malik, Mechanism of endothelin-1-induced pulmonary vasoconstriction. Circ. Res. 69(1), 157–164 (1991)

    Article  CAS  PubMed  Google Scholar 

  21. K. Nakanishi, F. Tajima, Y. Nakata, H. Osada, S. Tachibana, T. Kawai, C. Torikata, T. Suga, K. Takishima, T. Aurues, T. Ikeda, Expression of endothelin-1 in rats developing hypobaric hypoxia-induced pulmonary hypertension. Lab. Invest. 79(11), 1347–1357 (1999)

    CAS  PubMed  Google Scholar 

  22. D.J. Stewart, R.D. Levy, P. Cernacek, D. Langleben, Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Ann. Intern. Med. 114(6), 464–469 (1991)

    Article  CAS  PubMed  Google Scholar 

  23. S. Oparil, S.J. Chen, Q.C. Meng, T.S. Elton, M. Yano, Y.F. Chen, Endothelin-A receptor antagonist prevents acute hypoxia-induced pulmonary hypertension in the rat. Am. J. Physiol. 268(1 Pt 1), L95–L100 (1995)

    CAS  PubMed  Google Scholar 

  24. V.S. DiCarlo, S.J. Chen, Q.C. Meng, J. Durand, M. Yano, Y.F. Chen, S. Oparil, ETA-receptor antagonist prevents and reverses chronic hypoxia-induced pulmonary hypertension in rat. Am. J. Physiol. 269(5 Pt 1), L690–L697 (1995)

    CAS  PubMed  Google Scholar 

  25. S.T. Bonvallet, M.R. Zamora, K. Hasunuma, K. Sato, N. Hanasato, D. Anderson, K. Sato, T.J. Stelzner, BQ123, an ETA-receptor antagonist, attenuates hypoxic pulmonary hypertension in rats. Am. J. Physiol. 266(4 Pt 2), H1327–H1331 (1994)

    CAS  PubMed  Google Scholar 

  26. W. Johnson, A. Nohria, L. Garrett, J.C. Fang, J. Igo, M. Katai, P. Ganz, M.A. Creager, Contribution of endothelin to pulmonary vascular tone under normoxic and hypoxic conditions. Am. J. Physiol. Heart Circ. Physiol. 283(2), H568–H575 (2002). https://doi.org/10.1152/ajpheart.00099.2001

    Article  CAS  PubMed  Google Scholar 

  27. I. Pham, G. Wuerzner, J.P. Richalet, S. Peyrard, M. Azizi, Endothelin receptors blockade blunts hypoxia-induced increase in PAP in humans. Eur. J. Clin. Invest. 40(3), 195–202 (2010). https://doi.org/10.1111/j.1365-2362.2010.02254.x

    Article  CAS  PubMed  Google Scholar 

  28. P.A. Modesti, S. Vanni, M. Morabito, A. Modesti, M. Marchetta, T. Gamberi, F. Sofi, G. Savia, G. Mancia, G.F. Gensini, G. Parati, Role of endothelin-1 in exposure to high altitude: acute mountain sickness and endothelin-1 (ACME-1) study. Circulation 114(13), 1410–1416 (2006). https://doi.org/10.1161/CIRCULATIONAHA.105.605527

    Article  CAS  PubMed  Google Scholar 

  29. R.D. Seheult, K. Ruh, G.P. Foster, J.D. Anholm, Prophylactic bosentan does not improve exercise capacity or lower pulmonary artery systolic pressure at high altitude. Respir. Physiol. Neurobiol. 165(2–3), 123–130 (2009). https://doi.org/10.1016/j.resp.2008.10.005

    Article  CAS  PubMed  Google Scholar 

  30. R. Naeije, S. Huez, M. Lamotte, K. Retailleau, S. Neupane, D. Abramowicz, V. Faoro, Pulmonary artery pressure limits exercise capacity at high altitude. Eur. Respir. J. 36(5), 1049–1055 (2010). https://doi.org/10.1183/09031936.00024410

    Article  CAS  PubMed  Google Scholar 

  31. D. Kylhammar, G. Radegran, The principal pathways involved in the in vivo modulation of hypoxic pulmonary vasoconstriction, pulmonary arterial remodelling and pulmonary hypertension. Acta Physiol. 219(4), 728–756 (2017). https://doi.org/10.1111/apha.12749

    Article  CAS  Google Scholar 

  32. V.V. Kuzkov, M.Y. Kirov, M.A. Sovershaev, V.N. Kuklin, E.V. Suborov, K. Waerhaug, L.J. Bjertnaes, Extravascular lung water determined with single transpulmonary thermodilution correlates with the severity of sepsis-induced acute lung injury. Crit. Care. Med. 34(6), 1647–1653 (2006). https://doi.org/10.1097/01.CCM.0000218817.24208.2E

    Article  PubMed  Google Scholar 

  33. I. Kosmidou, D. Karmpaliotis, A.J. Kirtane, H.V. Barron, C.M. Gibson, Vascular endothelial growth factors in pulmonary edema: an update. J. Thromb. Thrombolysis 25(3), 259–264 (2008). https://doi.org/10.1007/s11239-007-0062-4

    Article  CAS  PubMed  Google Scholar 

  34. A.P. Comellas, A. Briva, Role of endothelin-1 in acute lung injury. Transl. Res. 153(6), 263–271 (2009). https://doi.org/10.1016/j.trsl.2009.02.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. I. Pham, G. Wuerzner, J.P. Richalet, S. Peyrard, M. Azizi, Bosentan effects in hypoxic pulmonary vasoconstriction: preliminary study in subjects with or without high altitude pulmonary edema-history. Pulm. Circ. 2(1), 28–33 (2012). https://doi.org/10.4103/2045-8932.94824

    Article  PubMed  PubMed Central  Google Scholar 

  36. C. Sartori, L. Vollenweider, B.M. Loffler, A. Delabays, P. Nicod, P. Bartsch, U. Scherrer, Exaggerated endothelin release in high-altitude pulmonary edema. Circulation 99(20), 2665–2668 (1999)

    Article  CAS  PubMed  Google Scholar 

  37. S.W. Allen, B.A. Chatfield, S.A. Koppenhafer, M.S. Schaffer, R.R. Wolfe, S.H. Abman, Circulating immunoreactive endothelin-1 in children with pulmonary hypertension. Association with acute hypoxic pulmonary vasoreactivity. Am. Rev. Respir. Dis. 148(2), 519–522 (1993). https://doi.org/10.1164/ajrccm/148.2.519

    Article  CAS  PubMed  Google Scholar 

  38. M.P. Schneider, E.I. Boesen, D.M. Pollock, Contrasting actions of endothelin ET(A) and ET(B) receptors in cardiovascular disease. Annu. Rev. Pharmacol. Toxicol. 47, 731–759 (2007). https://doi.org/10.1146/annurev.pharmtox.47.120505.105134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. B.K. Kramer, M. Bucher, P. Sandner, K.P. Ittner, G.A. Riegger, T. Ritthaler, A. Kurtz, Effects of hypoxia on growth factor expression in the rat kidney in vivo. Kidney Int. 51(2), 444–447 (1997)

    Article  CAS  PubMed  Google Scholar 

  40. K.U. Eckardt, W.M. Bernhardt, A. Weidemann, C. Warnecke, C. Rosenberger, M.S. Wiesener, C. Willam, Role of hypoxia in the pathogenesis of renal disease. Kidney Int. Suppl. 99, S46–S51 (2005). https://doi.org/10.1111/j.1523-1755.2005.09909.x

    Article  CAS  Google Scholar 

  41. D.E. Kohan, E. Padilla, Osmolar regulation of endothelin-1 production by rat inner medullary collecting duct. J. Clin. Invest. 91(3), 1235–1240 (1993). https://doi.org/10.1172/JCI116286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. V.H. Haase, Mechanisms of hypoxia responses in renal tissue. J. Am. Soc. Nephrol. 24(4), 537–541 (2013). https://doi.org/10.1681/ASN.2012080855

    Article  CAS  PubMed  Google Scholar 

  43. A. Nir, A.L. Clavell, D. Heublein, L.L. Aarhus, J.C. Burnett Jr., Acute hypoxia and endogenous renal endothelin. J. Am. Soc. Nephrol. 4(11), 1920–1924 (1994)

    CAS  PubMed  Google Scholar 

  44. J.B. Heimlich, J.S. Speed, C.J. Bloom, P.M. O’Connor, J.S. Pollock, D.M. Pollock, ET-1 increases reactive oxygen species following hypoxia and high-salt diet in the mouse glomerulus. Acta Physiol. 213(3), 722–730 (2015). https://doi.org/10.1111/apha.12397

    Article  CAS  Google Scholar 

  45. B. Kisch, Electron microscopy of the atrium of the heart. I. Guinea pig. Exp. Med. Surg. 14(2–3), 99–112 (1956)

    CAS  PubMed  Google Scholar 

  46. K. Kangawa, H. Matsuo, Purification and complete amino acid sequence of alpha-human atrial natriuretic polypeptide (alpha-hANP). Biochem. Biophys. Res. Commun. 118(1), 131–139 (1984)

    Article  CAS  PubMed  Google Scholar 

  47. Y. Saito, Roles of atrial natriuretic peptide and its therapeutic use. J. Cardiol. 56(3), 262–270 (2010)

    Article  PubMed  Google Scholar 

  48. K.S. Misono, J.S. Philo, T. Arakawa, C.M. Ogata, Y. Qiu, H. Ogawa, H.S. Young, Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase. FEBS J. 278(11), 1818–1829 (2011). https://doi.org/10.1111/j.1742-4658.2011.08083.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. L.R. Potter, Natriuretic peptide metabolism, clearance and degradation. FEBS J. 278(11), 1808–1817 (2011). https://doi.org/10.1111/j.1742-4658.2011.08082.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. O. Arjamaa, M. Nikinmaa, Hypoxia regulates the natriuretic peptide system. Int. J. Physiol. Pathophysiol. Pharmacol. 3(3), 191–201 (2011)

    CAS  PubMed  PubMed Central  Google Scholar 

  51. R.J. Winter, L. Zhao, T. Krausz, J.M. Hughes, Neutral endopeptidase 24.11 inhibition reduces pulmonary vascular remodeling in rats exposed to chronic hypoxia. Am. Rev. Respir. Dis. 144(6), 1342–1346 (1991). https://doi.org/10.1164/ajrccm/144.6.1342

    Article  CAS  PubMed  Google Scholar 

  52. N.B. Standen, J.M. Quayle, K+ channel modulation in arterial smooth muscle. Acta Physiol. Scand. 164(4), 549–557 (1998). https://doi.org/10.1046/j.1365-201X.1998.00433.x

    Article  CAS  PubMed  Google Scholar 

  53. M. Kuhn, Structure, regulation, and function of mammalian membrane guanylyl cyclase receptors, with a focus on guanylyl cyclase-A. Circ. Res. 93(8), 700–709 (2003). https://doi.org/10.1161/01.RES.0000094745.28948.4D

    Article  CAS  PubMed  Google Scholar 

  54. Y.F. Chen, Atrial natriuretic peptide in hypoxia. Peptides 26(6), 1068–1077 (2005). https://doi.org/10.1016/j.peptides.2004.08.030

    Article  CAS  PubMed  Google Scholar 

  55. O. Pauvert, S. Bonnet, E. Rousseau, R. Marthan, J.P. Savineau, Sildenafil alters calcium signaling and vascular tone in pulmonary arteries from chronically hypoxic rats. Am. J. Physiol. Lung Cell. Mol. Physiol. 287(3), L577–L583 (2004). https://doi.org/10.1152/ajplung.00449.2003

    Article  CAS  PubMed  Google Scholar 

  56. M. Gomberg-Maitland, V. McLaughlin, M. Gulati, S. Rich, Efficacy and safety of sildenafil added to treprostinil in pulmonary hypertension. Am. J. Cardiol. 96(9), 1334–1336 (2005). https://doi.org/10.1016/j.amjcard.2005.06.083

    Article  CAS  PubMed  Google Scholar 

  57. H.H. Leuchte, M. Schwaiblmair, R.A. Baumgartner, C.F. Neurohr, T. Kolbe, J. Behr, Hemodynamic response to sildenafil, nitric oxide, and iloprost in primary pulmonary hypertension. Chest 125(2), 580–586 (2004)

    Article  CAS  PubMed  Google Scholar 

  58. D. Wang, S. Oparil, J.A. Feng, P. Li, G. Perry, L.B. Chen, M. Dai, S.W. John, Y.F. Chen, Effects of pressure overload on extracellular matrix expression in the heart of the atrial natriuretic peptide-null mouse. Hypertension 42(1), 88–95 (2003). https://doi.org/10.1161/01.HYP.0000074905.22908.A6

    Article  CAS  PubMed  Google Scholar 

  59. Y.S. Chun, J.Y. Hyun, Y.G. Kwak, I.S. Kim, C.H. Kim, E. Choi, M.S. Kim, J.W. Park, Hypoxic activation of the atrial natriuretic peptide gene promoter through direct and indirect actions of hypoxia-inducible factor-1. Biochem. J. 370(Pt 1), 149–157 (2003). https://doi.org/10.1042/BJ20021087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Q.L. Zhang, B.R. Cui, H.Y. Li, P. Li, L. Hong, L.P. Liu, D.Z. Ding, X. Cui, MAPK and PI3K pathways regulate hypoxia-induced atrial natriuretic peptide secretion by controlling HIF-1 alpha expression in beating rabbit atria. Biochem. Biophys. Res. Commun. 438(3), 507–512 (2013). https://doi.org/10.1016/j.bbrc.2013.07.106

    Article  CAS  PubMed  Google Scholar 

  61. W. Forssmann, M. Meyer, K. Forssmann, The renal urodilatin system: clinical implications. Cardiovasc. Res. 51(3), 450–462 (2001)

    Article  CAS  PubMed  Google Scholar 

  62. B. Haditsch, A. Roessler, P. Krisper, H. Frisch, H.G. Hinghofer-Szalkay, N. Goswami, Volume regulation and renal function at high altitude across gender. PLoS. One 10(3), e0118730 (2015). https://doi.org/10.1371/journal.pone.0118730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. R.G. Westendorp, A.N. Roos, H.G. van der Hoeven, M.Y. Tjiong, R. Simons, M. Frolich, J.H. Souverijn, A.E. Meinders, Atrial natriuretic peptide improves pulmonary gas exchange in subjects exposed to hypoxia. Am. Rev. Respir. Dis. 148(2), 304–309 (1993). https://doi.org/10.1164/ajrccm/148.2.304

    Article  CAS  PubMed  Google Scholar 

  64. T.J. Tunny, J. van Gelder, R.D. Gordon, S.A. Klemm, S.M. Hamlet, W.L. Finn, G.M. Carney, C. Brand-Maher, Effects of altitude on atrial natriuretic peptide: the Bicentennial Mount Everest expedition. Clin. Exp. Pharmacol. Physiol. 16(4), 287–291 (1989)

    Article  CAS  PubMed  Google Scholar 

  65. A. Kawashima, K. Kubo, K. Hirai, S. Yoshikawa, Y. Matsuzawa, T. Kobayashi, Plasma levels of atrial natriuretic peptide under acute hypoxia in normal subjects. Respir. Physiol. 76(1), 79–91 (1989)

    Article  CAS  PubMed  Google Scholar 

  66. R.I. Cargill, B.J. Lipworth, Acute effects of ANP and BNP on hypoxic pulmonary vasoconstriction in humans. Br. J. Clin. Pharmacol. 40(6), 585–590 (1995)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. M.C. Chappell, Biochemical evaluation of the renin-angiotensin system: the good, bad, and absolute? Am. J. Physiol. Heart Circ. Physiol. 310(2), H137–H152 (2016). https://doi.org/10.1152/ajpheart.00618.2015

    Article  PubMed  Google Scholar 

  68. L.C. Roksnoer, K. Verdonk, A.H. van den Meiracker, E.J. Hoorn, R. Zietse, A.H. Danser, Urinary markers of intrarenal renin-angiotensin system activity in vivo. Curr. Hypertens. Rep. 15(2), 81–88 (2013). https://doi.org/10.1007/s11906-012-0326-z

    Article  CAS  PubMed  Google Scholar 

  69. K.E. Bernstein, F.S. Ong, W.L. Blackwell, K.H. Shah, J.F. Giani, R.A. Gonzalez-Villalobos, X.Z. Shen, S. Fuchs, R.M. Touyz, A modern understanding of the traditional and nontraditional biological functions of angiotensin-converting enzyme. Pharmacol. Rev. 65(1), 1–46 (2013). https://doi.org/10.1124/pr.112.006809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. J.T. August, D.H. Nelson, G.W. Thorn, Aldosterone. N. Engl. J. Med. 259(19), 917–923 (1958). https://doi.org/10.1056/NEJM195811062591907. contd

    Article  CAS  PubMed  Google Scholar 

  71. P.K. Mehta, K.K. Griendling, Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am. J. Physiol. Cell. Physiol. 292(1), C82–C97 (2007). https://doi.org/10.1152/ajpcell.00287.2006

    Article  CAS  PubMed  Google Scholar 

  72. E. Kaschina, T. Unger, Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press. 12(2), 70–88 (2003)

    Article  CAS  PubMed  Google Scholar 

  73. Y. Imai, K. Kuba, T. Ohto-Nakanishi, J.M. Penninger, Angiotensin-converting enzyme 2 (ACE2) in disease pathogenesis. Circ. J. 74(3), 405–410 (2010)

    Article  CAS  PubMed  Google Scholar 

  74. K.B. Brosnihan, L.A. Neves, M.C. Chappell, Does the angiotensin-converting enzyme (ACE)/ACE2 balance contribute to the fate of angiotensin peptides in programmed hypertension? Hypertension 46(5), 1097–1099 (2005). https://doi.org/10.1161/01.HYP.0000185149.56516.0a

    Article  CAS  PubMed  Google Scholar 

  75. S. Wakahara, T. Konoshita, S. Mizuno, M. Motomura, C. Aoyama, Y. Makino, N. Kato, I. Koni, I. Miyamori, Synergistic expression of angiotensin-converting enzyme (ACE) and ACE2 in human renal tissue and confounding effects of hypertension on the ACE to ACE2 ratio. Endocrinology 148(5), 2453–2457 (2007). https://doi.org/10.1210/en.2006-1287

    Article  CAS  PubMed  Google Scholar 

  76. C.N. Bradford, D.R. Ely, M.K. Raizada, Targeting the vasoprotective axis of the renin-angiotensin system: a novel strategic approach to pulmonary hypertensive therapy. Curr. Hypertens. Rep. 12(4), 212–219 (2010). https://doi.org/10.1007/s11906-010-0122-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. R. Zhang, Y. Wu, M. Zhao, C. Liu, L. Zhou, S. Shen, S. Liao, K. Yang, Q. Li, H. Wan, Role of HIF-1alpha in the regulation ACE and ACE2 expression in hypoxic human pulmonary artery smooth muscle cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 297(4), L631–L640 (2009). https://doi.org/10.1152/ajplung.90415.2008

    Article  CAS  PubMed  Google Scholar 

  78. L.J. Mullins, B.R. Conway, R.I. Menzies, L. Denby, J.J. Mullins, Renal disease pathophysiology and treatment: contributions from the rat. Dis. Model. Mech. 9(12), 1419–1433 (2016). https://doi.org/10.1242/dmm.027276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. J. Loeffler, J. Stockigt, W. Ganong, Effect of alpha-and beta-adrenergic blocking agents on the increase in renin secretion produced by stimulation of the renal nerves. Neuroendocrinology 10(3), 129–138 (1972)

    Article  CAS  PubMed  Google Scholar 

  80. M. Nangaku, T. Fujita, Activation of the renin-angiotensin system and chronic hypoxia of the kidney. Hypertens. Res. 31(2), 175–184 (2008). https://doi.org/10.1291/hypres.31.175

    Article  PubMed  Google Scholar 

  81. H. Matsui, T. Shimosawa, K. Itakura, X. Guanqun, K. Ando, T. Fujita, Adrenomedullin can protect against pulmonary vascular remodeling induced by hypoxia. Circulation 109(18), 2246–2251 (2004). https://doi.org/10.1161/01.CIR.0000127950.13380.FD

    Article  CAS  PubMed  Google Scholar 

  82. C. Ruster, G. Wolf, Renin-angiotensin-aldosterone system and progression of renal disease. J. Am. Soc. Nephrol. 17(11), 2985–2991 (2006). https://doi.org/10.1681/ASN.2006040356

    Article  CAS  PubMed  Google Scholar 

  83. S. Srivastava, S. Dwivedi, Significance of renin angiotensin aldosterone system (RAAS) pathway in high altitude pulmonary edema (HAPE) susceptibility. J. Clin. Mol. Endocrinol 1(3), 1–4 (2016).

    Google Scholar 

  84. E.C. Fletcher, N. Orolinova, M. Bader, Blood pressure response to chronic episodic hypoxia: the renin-angiotensin system. J. Appl. Physiol. 92(2), 627–633 (2002). https://doi.org/10.1152/japplphysiol.000152.2001

    Article  CAS  PubMed  Google Scholar 

  85. I. Hubloue, B. Rondelet, F. Kerbaul, D. Biarent, G.M. Milani, M. Staroukine, P. Bergmann, R. Naeije, M. Leeman, Endogenous angiotensin II in the regulation of hypoxic pulmonary vasoconstriction in anaesthetized dogs. Crit. Care 8(4), R163–R171 (2004). https://doi.org/10.1186/cc2860

    Article  PubMed  PubMed Central  Google Scholar 

  86. K. Manotham, B. Ongvilawan, P. Urusopone, S. Chetsurakarn, J. Tanamai, P. Limkuansuwan, K. Tungsanga, S. Eiam-Ong, Angiotensin II receptor blocker partially ameliorated intrarenal hypoxia in chronic kidney disease patients: a pre-/post-study. Intern. Med. J. 42(4), e33–e37 (2012)

    Article  CAS  PubMed  Google Scholar 

  87. N.J. Marcus, Y.L. Li, C.E. Bird, H.D. Schultz, B.J. Morgan, Chronic intermittent hypoxia augments chemoreflex control of sympathetic activity: role of the angiotensin II type 1 receptor. Respir. Physiol. Neurobiol. 171(1), 36–45 (2010). https://doi.org/10.1016/j.resp.2010.02.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. M.C. Lansang, S.Y. Osei, D.A. Price, N.D. Fisher, N.K. Hollenberg, Renal hemodynamic and hormonal responses to the angiotensin II antagonist candesartan. Hypertension 36(5), 834–838 (2000)

    Article  CAS  PubMed  Google Scholar 

  89. N.R. Prabhakar, G.K. Kumar, Mechanisms of sympathetic activation and blood pressure elevation by intermittent hypoxia. Respir. Physiol. Neurobiol. 174(1–2), 156–161 (2010). https://doi.org/10.1016/j.resp.2010.08.021

    Article  PubMed  PubMed Central  Google Scholar 

  90. V. Pialoux, G.E. Foster, S.B. Ahmed, A.E. Beaudin, P.J. Hanly, M.J. Poulin, Losartan abolishes oxidative stress induced by intermittent hypoxia in humans. J. Physiol. 589(Pt 22), 5529–5537 (2011). https://doi.org/10.1113/jphysiol.2011.218156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. G.E. Foster, P.J. Hanly, S.B. Ahmed, A.E. Beaudin, V. Pialoux, M.J. Poulin, Intermittent hypoxia increases arterial blood pressure in humans through a renin-angiotensin system-dependent mechanism. Hypertension 56(3), 369–377 (2010). https://doi.org/10.1161/HYPERTENSIONAHA.110.152108

    Article  CAS  PubMed  Google Scholar 

  92. R. Tamisier, J.L. Pepin, J. Remy, J.P. Baguet, J.A. Taylor, J.W. Weiss, P. Levy, 14 nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans. Eur. Respir. J. 37(1), 119–128 (2011). https://doi.org/10.1183/09031936.00204209

    Article  CAS  PubMed  Google Scholar 

  93. G.S. Gilmartin, M. Lynch, R. Tamisier, J.W. Weiss, Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity. Am. J. Physiol. Heart Circ. Physiol. 299(3), H925–H931 (2010). https://doi.org/10.1152/ajpheart.00253.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. G. Bao, N. Metreveli, R. Li, A. Taylor, E.C. Fletcher, Blood pressure response to chronic episodic hypoxia: role of the sympathetic nervous system. J. Appl. Physiol. 83(1), 95–101 (1997)

    Article  CAS  PubMed  Google Scholar 

  95. E.C. Fletcher, J. Lesske, J. Culman, C.C. Miller, T. Unger, Sympathetic denervation blocks blood pressure elevation in episodic hypoxia. Hypertension 20(5), 612–619 (1992)

    Article  CAS  PubMed  Google Scholar 

  96. E.C. Fletcher, G. Bao, R. Li, Renin activity and blood pressure in response to chronic episodic hypoxia. Hypertension 34(2), 309–314 (1999)

    Article  CAS  PubMed  Google Scholar 

  97. S.Y. Lam, P.S. Leung, A locally generated angiotensin system in rat carotid body. Regul. Pept. 107(1–3), 97–103 (2002)

    Article  CAS  PubMed  Google Scholar 

  98. S.Y. Lam, Y. Liu, K.M. Ng, E.C. Liong, G.L. Tipoe, P.S. Leung, M.L. Fung, Upregulation of a local renin-angiotensin system in the rat carotid body during chronic intermittent hypoxia. Exp. Physiol. 99(1), 220–231 (2014). https://doi.org/10.1113/expphysiol.2013.074591

    Article  CAS  PubMed  Google Scholar 

  99. M. Boone, P.M. Deen, Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption. Pflug. Arch. 456(6), 1005–1024 (2008). https://doi.org/10.1007/s00424-008-0498-1

    Article  CAS  Google Scholar 

  100. M.E. Alfie, S. Alim, D. Mehta, E.G. Shesely, O.A. Carretero, An enhanced effect of arginine vasopressin in bradykinin B2 receptor null mutant mice. Hypertension 33(6), 1436–1440 (1999)

    Article  CAS  PubMed  Google Scholar 

  101. C.W. Bourque, S.H. Oliet, D. Richard, Osmoreceptors, osmoreception, and osmoregulation. Front. Neuroendocrinol. 15(3), 231–274 (1994). https://doi.org/10.1006/frne.1994.1010

    Article  CAS  PubMed  Google Scholar 

  102. M.A. Knepper, Molecular physiology of urinary concentrating mechanism: regulation of aquaporin water channels by vasopressin. Am. J. Physiol. 272(1 Pt 2), F3–F12 (1997)

    CAS  PubMed  Google Scholar 

  103. C.M. Maresh, W.J. Kraemer, D.A. Judelson, J.L. VanHeest, L. Trad, J.M. Kulikowich, K.L. Goetz, A. Cymerman, A.J. Hamilton, Effects of high altitude and water deprivation on arginine vasopressin release in men. Am. J. Physiol. Endocrinol. Metab. 286(1), E20–E24 (2004). https://doi.org/10.1152/ajpendo.00332.2003

    Article  CAS  PubMed  Google Scholar 

  104. G. Ramirez, D. Pineda, P.A. Bittle, H. Rabb, R. Rosen, D. Vesely, S. Sasaki, Partial renal resistance to arginine vasopressin as an adaptation to high altitude living. Aviat. Space Environ. Med. 69(1), 58–65 (1998)

    CAS  PubMed  Google Scholar 

  105. A. Takamata, H. Nose, T. Kinoshita, M. Hirose, T. Itoh, T. Morimoto, Effect of acute hypoxia on vasopressin release and intravascular fluid during dynamic exercise in humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. 279(1), R161–R168 (2000)

    Article  CAS  PubMed  Google Scholar 

  106. F.D. Blume, S.J. Boyer, L.E. Braverman, A. Cohen, J. Dirkse, J.P. Mordes, Impaired osmoregulation at high altitude: studies on Mt Everest. Jama 252(4), 524–526 (1984)

    Article  CAS  PubMed  Google Scholar 

  107. L. Ostergaard, A. Rudiger, S. Wellmann, E. Gammella, B. Beck-Schimmer, J. Struck, M. Maggiorini, M. Gassmann, Arginine-vasopressin marker copeptin is a sensitive plasma surrogate of hypoxic exposure. Hypoxia 2, 143–151 (2014). https://doi.org/10.2147/HP.S57894

    Article  PubMed  PubMed Central  Google Scholar 

  108. R.L. Cosby, A.M. Sophocles, J.A. Durr, C.L. Perrinjaquet, B. Yee, R.W. Schrier, Elevated plasma atrial natriuretic factor and vasopressin in high-altitude pulmonary edema. Ann. Intern. Med. 109(10), 796–799 (1988)

    Article  CAS  PubMed  Google Scholar 

  109. P. Bartsch, M. Maggiorini, W. Schobersberger, S. Shaw, W. Rascher, J. Girard, P. Weidmann, O. Oelz, Enhanced exercise-induced rise of aldosterone and vasopressin preceding mountain sickness. J. Appl. Physiol. 71(1), 136–143 (1991)

    Article  CAS  PubMed  Google Scholar 

  110. O. Pak, A. Aldashev, D. Welsh, A. Peacock, The effects of hypoxia on the cells of the pulmonary vasculature. Eur. Respir. J. 30(2), 364–372 (2007). https://doi.org/10.1183/09031936.00128706

    Article  CAS  PubMed  Google Scholar 

  111. C. Fonseca, D. Abraham, E.A. Renzoni, Endothelin in pulmonary fibrosis. Am. J. Respir. Cell. Mol. Biol. 44(1), 1–10 (2011). https://doi.org/10.1165/rcmb.2009-0388TR

    Article  CAS  PubMed  Google Scholar 

  112. N.J. Davie, E.V. Gerasimovskaya, S.E. Hofmeister, A.P. Richman, P.L. Jones, J.T. Reeves, K.R. Stenmark, Pulmonary artery adventitial fibroblasts cooperate with vasa vasorum endothelial cells to regulate vasa vasorum neovascularization: a process mediated by hypoxia and endothelin-1. Am. J. Pathol. 168(6), 1793–1807 (2006). https://doi.org/10.2353/ajpath.2006.050754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. L.A. Shimoda, S.S. Laurie, HIF and pulmonary vascular responses to hypoxia. J. Appl. Physiol. 116(7), 867–874 (2014). https://doi.org/10.1152/japplphysiol.00643.2013

    Article  CAS  PubMed  Google Scholar 

  114. P.M. Hassoun, V. Thappa, M.J. Landman, B.L. Fanburg, Endothelin 1: mitogenic activity on pulmonary artery smooth muscle cells and release from hypoxic endothelial cells. Proc. Soc. Exp. Biol. Med. Soc. Exp. Biol. Med. 199(2), 165–170 (1992)

    Article  CAS  Google Scholar 

  115. Y. Fan, L. Wang, C. Liu, H. Zhu, L. Zhou, Y. Wang, X. Wu, Q. Li, Local renin-angiotensin system regulates hypoxia-induced vascular endothelial growth factor synthesis in mesenchymal stem cells. Int. J. Clin. Exp. Pathol. 8(3), 2505–2514 (2015)

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Y. Zhang, J. Lv, H. Guo, X. Wei, W. Li, Z. Xu, Hypoxia-induced proliferation in mesenchymal stem cells and angiotensin II-mediated PI3K/AKT pathway. Cell. Biochem. Funct. 33(2), 51–58 (2015). https://doi.org/10.1002/cbf.3080

    Article  CAS  PubMed  Google Scholar 

  117. N.W. Morrell, P.D. Upton, M.A. Higham, M.H. Yacoub, J.M. Polak, J. Wharton, Angiotensin II stimulates proliferation of human pulmonary artery smooth muscle cells via the AT1 receptor. Chest 114(1 Suppl), 90S–91S (1998)

    Article  CAS  PubMed  Google Scholar 

  118. S. Krick, J. Hanze, B. Eul, R. Savai, U. Seay, F. Grimminger, J. Lohmeyer, W. Klepetko, W. Seeger, F. Rose, Hypoxia-driven proliferation of human pulmonary artery fibroblasts: cross-talk between HIF-1alpha and an autocrine angiotensin system. FASEB J. 19(7), 857–859 (2005). https://doi.org/10.1096/fj.04-2890fje

    Article  CAS  PubMed  Google Scholar 

  119. K.R. Stenmark, D. Bouchey, R. Nemenoff, E.C. Dempsey, M. Das, Hypoxia-induced pulmonary vascular remodeling: contribution of the adventitial fibroblasts. Physiol. Res. 49(5), 503–517 (2000)

    CAS  PubMed  Google Scholar 

  120. M. Humbert, N.W. Morrell, S.L. Archer, K.R. Stenmark, M.R. MacLean, I.M. Lang, B.W. Christman, E.K. Weir, O. Eickelberg, N.F. Voelkel, M. Rabinovitch, Cellular and molecular pathobiology of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 43(12 Suppl S), 13S–24S (2004). https://doi.org/10.1016/j.jacc.2004.02.029

    Article  CAS  PubMed  Google Scholar 

  121. N.J. Davie, J.T. Crossno Jr., M.G. Frid, S.E. Hofmeister, J.T. Reeves, D.M. Hyde, T.C. Carpenter, J.A. Brunetti, I.K. McNiece, K.R. Stenmark, Hypoxia-induced pulmonary artery adventitial remodeling and neovascularization: contribution of progenitor cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 286(4), L668–L678 (2004). https://doi.org/10.1152/ajplung.00108.2003

    Article  CAS  PubMed  Google Scholar 

  122. M. Vogler, S. Vogel, S. Krull, K. Farhat, P. Leisering, S. Lutz, C.M. Wuertz, D.M. Katschinski, A. Zieseniss, Hypoxia modulates fibroblastic architecture, adhesion and migration: a role for HIF-1alpha in cofilin regulation and cytoplasmic actin distribution. PLoS. One 8(7), e69128 (2013). https://doi.org/10.1371/journal.pone.0069128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. D.M. Gilkes, S. Bajpai, P. Chaturvedi, D. Wirtz, G.L. Semenza, Hypoxia-inducible factor 1 (HIF-1) promotes extracellular matrix remodeling under hypoxic conditions by inducing P4HA1, P4HA2, and PLOD2 expression in fibroblasts. J. Biol. Chem. 288(15), 10819–10829 (2013). https://doi.org/10.1074/jbc.M112.442939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. S. Mizuno, H.J. Bogaard, N.F. Voelkel, Y. Umeda, M. Kadowaki, S. Ameshima, I. Miyamori, T. Ishizaki, Hypoxia regulates human lung fibroblast proliferation via p53-dependent and -independent pathways. Respir. Res. 10, 17 (2009). https://doi.org/10.1186/1465-9921-10-17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Y. Horino, S. Takahashi, T. Miura, Y. Takahashi, Prolonged hypoxia accelerates the posttranscriptional process of collagen synthesis in cultured fibroblasts. Life Sci. 71(26), 3031–3045 (2002)

    Article  CAS  PubMed  Google Scholar 

  126. L. Rosano, F. Spinella, A. Bagnato, Endothelin 1 in cancer: biological implications and therapeutic opportunities. Nat. Rev. Cancer 13(9), 637–651 (2013). https://doi.org/10.1038/nrc3546

    Article  CAS  PubMed  Google Scholar 

  127. A. Bouallegue, G.B. Daou, A.K. Srivastava, Endothelin-1-induced signaling pathways in vascular smooth muscle cells. Curr. Vasc. Pharmacol. 5(1), 45–52 (2007)

    Article  CAS  PubMed  Google Scholar 

  128. G.E. Morris, C.P. Nelson, N.B. Standen, R.A. Challiss, J.M. Willets, Endothelin signalling in arterial smooth muscle is tightly regulated by G protein-coupled receptor kinase 2. Cardiovasc. Res. 85(3), 424–433 (2010). https://doi.org/10.1093/cvr/cvp310

    Article  CAS  PubMed  Google Scholar 

  129. M.B. Anand-Srivastava, Natriuretic peptide receptor-C signaling and regulation. Peptides 26(6), 1044–1059 (2005). https://doi.org/10.1016/j.peptides.2004.09.023

    Article  CAS  PubMed  Google Scholar 

  130. N.E. Zois, E.D. Bartels, I. Hunter, B.S. Kousholt, L.H. Olsen, J.P. Goetze, Natriuretic peptides in cardiometabolic regulation and disease. Nat. Rev. Cardiol. 11(7), 403–412 (2014). https://doi.org/10.1038/nrcardio.2014.64

    Article  CAS  PubMed  Google Scholar 

  131. K.N. Pandey, Guanylyl cyclase/natriuretic peptide receptor-A signaling antagonizes phosphoinositide hydrolysis, Ca(2+) release, and activation of protein kinase C. Front. Mol. Neurosci. 7, 75 (2014). https://doi.org/10.3389/fnmol.2014.00075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. L.R. Potter, A.R. Yoder, D.R. Flora, L.K. Antos, D.M. Dickey, Natriuretic peptides: their structures, receptors, physiologic functions and therapeutic applications. Handb. Exp. Pharmacol. 191, 341–366 (2009). https://doi.org/10.1007/978-3-540-68964-5_15

    Article  CAS  Google Scholar 

  133. D.F. Guo, Y.L. Sun, P. Hamet, T. Inagami, The angiotensin II type 1 receptor and receptor-associated proteins. Cell. Res. 11(3), 165–180 (2001). https://doi.org/10.1038/sj.cr.7290083

    Article  CAS  PubMed  Google Scholar 

  134. S. Higuchi, H. Ohtsu, H. Suzuki, H. Shirai, G.D. Frank, S. Eguchi, Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology. Clin. Sci. 112(8), 417–428 (2007). https://doi.org/10.1042/CS20060342

    Article  CAS  PubMed  Google Scholar 

  135. S. AbdAlla, H. Lother, A.M. Abdel-tawab, U. Quitterer, The angiotensin II AT2 receptor is an AT1 receptor antagonist. J. Biol. Chem. 276(43), 39721–39726 (2001). https://doi.org/10.1074/jbc.M105253200

    Article  CAS  PubMed  Google Scholar 

  136. L. Gendron, M.D. Payet, N. Gallo-Payet, The angiotensin type 2 receptor of angiotensin II and neuronal differentiation: from observations to mechanisms. J. Mol. Endocrinol. 31(3), 359–372 (2003)

    Article  CAS  PubMed  Google Scholar 

  137. J.D. Stockand, Vasopressin regulation of renal sodium excretion. Kidney Int. 78(9), 849–856 (2010). https://doi.org/10.1038/ki.2010.276

    Article  CAS  PubMed  Google Scholar 

  138. D.A. Ausiello, K.L. Skorecki, A.S. Verkman, J.V. Bonventre, Vasopressin signaling in kidney cells. Kidney Int. 31(2), 521–529 (1987)

    Article  CAS  PubMed  Google Scholar 

  139. J.D. Stockand, New ideas about aldosterone signaling in epithelia. American journal of physiology. Ren. Physiol. 282(4), F559–F576 (2002). https://doi.org/10.1152/ajprenal.00320.2001

    Article  Google Scholar 

  140. M. Briet, E.L. Schiffrin, Aldosterone: effects on the kidney and cardiovascular system. Nat. Rev. Nephrol. 6(5), 261–273 (2010). https://doi.org/10.1038/nrneph.2010.30

    Article  CAS  PubMed  Google Scholar 

  141. C. Grossmann, M. Gekle, New aspects of rapid aldosterone signaling. Mol. Cell. Endocrinol. 308(1–2), 53–62 (2009). https://doi.org/10.1016/j.mce.2009.02.005

    Article  CAS  PubMed  Google Scholar 

  142. R. Dooley, B.J. Harvey, W. Thomas, Non-genomic actions of aldosterone: from receptors and signals to membrane targets. Mol. Cell. Endocrinol. 350(2), 223–234 (2012). https://doi.org/10.1016/j.mce.2011.07.019

    Article  CAS  PubMed  Google Scholar 

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    Priya Gaur, Supriya Saini, Praveen Vats & Bhuvnesh Kumar

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Gaur, P., Saini, S., Vats, P. et al. Regulation, signalling and functions of hormonal peptides in pulmonary vascular remodelling during hypoxia. Endocrine 59, 466–480 (2018). https://doi.org/10.1007/s12020-018-1529-0

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