Sustained therapeutic hypercapnia attenuates pulmonary arterial Rho-kinase activity and ameliorates chronic hypoxic pulmonary hypertension in juvenile rats

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 302, Issue 12, 2012, Pages 2599-2611

  Peng, Gary ^a   Ivanovska, Julijana ^a   Kantores, Crystal ^a   van Vliet, Todd ^a,b   Engelberts, Doreen ^a   Kavanagh, Brian P ^a,b,c   Enomoto, Masahiro ^a   Belik, Jaques ^a,b,c   Jain, Amish ^a,b,c   Mcnamara, Patrick J ^a,b,c   Jankov, Robert P ^a  

^a HOSPITAL FOR SICK CHILDREN RESEARCH INSTITUTE   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c UNIVERSITY OF TORONTO   (Canada)

Author keywords

Carbon dioxide; Hypoxia; Nitric oxide; Protein kinase G; RhoA

Indexed keywords

4 (1 AMINOETHYL) N (4 PYRIDYL)CYCLOHEXANECARBOXAMIDE; CYCLIC GMP; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; PHOSPHODIESTERASE; PROTEIN KINASE; RHO KINASE; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTERY RESISTANCE; ARTICLE; BLOOD VESSEL WALL; CARBON DIOXIDE BREATHING; CHRONIC DISEASE; CHRONIC HYPOXIC PULMONARY HYPERTENSION; CONTROLLED STUDY; HEART RIGHT VENTRICLE HYPERTROPHY; HYPOXIA; LUNG ARTERY PRESSURE; LUNG VASCULAR RESISTANCE; NONHUMAN; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RAT; SMOOTH MUSCLE FIBER; SYSTOLIC BLOOD PRESSURE; THERAPEUTIC HYPERCAPNIA;

ANIMALS; ANOXIA; CARBON DIOXIDE; CYCLIC GMP-DEPENDENT PROTEIN KINASES; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 5; HYPERTENSION, PULMONARY; LUNG; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, SMOOTH MUSCLE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE III; PULMONARY ARTERY; RATS; RHO-ASSOCIATED KINASES; RHOA GTP-BINDING PROTEIN; SIGNAL TRANSDUCTION; VASODILATION;

EID: 84862538718     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.01180.2011     Document Type: Article

References (75)

1. Abe K, Shimokawa H, Morikawa K, Uwatoku T, Oi K, Matsumoto Y, Hattori T, Nakashima Y, Kaibuchi K, Sueishi K, Takeshit A. Long-term treatment with a Rho-kinase inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats. Circ Res 94: 385-393, 2004.
2. Ambalavanan N, Mariani G, Bulger A, Philips IJ. Role of nitric oxide in regulating neonatal porcine pulmonary artery smooth muscle cell proliferation. Biol Neonate 76: 291-300, 1999.
3. Baudouin SV, Evans TW. Action of carbon dioxide on hypoxic pulmonary vasoconstriction in the rat lung: evidence against specific endothelium-derived relaxing factor-mediated vasodilation. Crit Care Med 21: 740-746, 1993.
4. Belik J, Stevens D, Pan J, McIntyre BA, Kantores C, Ivanovska J, Xu EZ, Ibrahim C, Panama BK, Backx PH, McNamara PJ, Jankov RP. Pulmonary vascular and cardiac effects of peroxynitrite decomposition in newborn rats. Free Rad Biol Med 49: 1306-1314, 2010.
5. Belik J, Stevens D, Pan J, Shehnaz D, Ibrahim C, Kantores C, Ivanovska J, Grasemann H, Jankov RP. Chronic hypercapnia down- regulates arginase expression and activity and increases pulmonary arterial smooth muscle relaxation in the newborn rat. Am J Physiol Lung Cell Mol Physiol 297: L777-L784, 2009.
6. 2+ sensitivity, and hypertension development in mice. Circulation 124: 1819-1829, 2011.
7. Cardenas VJ, Zwischenberger JB, Tao W, Nguyen PD, Schroeder T, Traber LD, Traber DL, Bidani A. Correction of blood pH attenuates changes in hemodynamics and organ blood flow during permissive hyper-capnia. Crit Care Med 24: 827-834, 1996.
8. Casey DB, Badejo AM, Dhaliwal JS, Sikora JL, Fokin A, Golwala NH, Greco AJ, Murthy SN, Nossaman BD, Hyman AL, Kadowitz PJ. Analysis of responses to the Rho-kinase inhibitor Y-27632 in the pulmonary and systemic vascular bed of the rat. Am J Physiol Heart Circ Physiol 299: H184-H192, 2010.
9. Caslin A, Heath D, Smith P. Influence of hypobaric hypoxia in infancy on the subsequent development of vasoconstrictive pulmonary vascular disease in the Wistar albino rat. J Pathol 163: 133-141, 1991.
10. Chovanec M, Novotna J, Wilhelm J, Hampl V, Vizek M, Herget J. Hypercapnia attenuates hypoxic pulmonary hypertension by inhibiting lung radical injury. Physiol Res 58, Suppl 2: S79-S85, 2009.
11. Chuang IC, Dong HP, Yang RC, Wang TH, Tsai JH, Yang PH, Huang MS. Effect of carbon dioxide on pulmonary vascular tone at various pulmonary arterial pressure levels induced by endothelin-1. Lung 188: 199-207, 2010.
12. Chuang IC, Yang RC, Chou SH, Huang LR, Tsai TN, Dong HP, Huang MS. Effect of carbon dioxide inhalation on pulmonary hypertension induced by increased blood flow and hypoxia. Kaohsiung J Med Sci 27: 336-343, 2011.
13. Chung HH, Dai ZK, Wu BN, Yeh JL, Chai CY, Chu KS, Liu CP, Chen IJ. The xanthine derivative KMUP-1 inhibits models of pulmonary artery hypertension via increased NO and cGMP-dependent inhibition of RhoA/Rho kinase. Br J Pharmacol 160: 971-986, 2010.
14. Dakshinamurti S. Regulation of myosin light chain phosphatase and pulmonary arterial relaxation. Can J Physiol Pharmacol 83: 893-898, 2005.
15. Emery CJ, Sloan PJ, Mohammed FH, Barer GR. The action of hypercapnia during hypoxia on pulmonary vessels. Bull Eur Physiopathol Respir 13: 763-776, 1977.
16. Fagan KA, Oka M, Bauer NR, Gebb SA, Ivy DD, Morris KG, McMurtry IF. Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of Rho-kinase. Am J Physiol Lung Cell Mol Physiol 287: L656-L664, 2004.
17. Feng J, Ito M, Ichikawa K, Isaka N, Nishikawa M, Hartshorne DJ, Nakano T. Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle myosin phosphatase. J Biol Chem 274: 37385-37390, 1999.
18. Gao Y, Portugal AD, Liu J, Negash S, Zhou W, Tian J, Xiang R, Longo LD, Raj JU. Preservation of cGMP-induced relaxation of pulmonary veins of fetal lambs exposed to chronic high altitude hypoxia: role of PKG and Rho kinase. Am J Physiol Lung Cell Mol Physiol 295: L889-L896, 2008.
19. Gao Y, Portugal AD, Negash S, Zhou W, Longo LD, Usha JU. Role of Rho kinases in PKG-mediated relaxation of pulmonary arteries of fetal lambs exposed to chronic high altitude hypoxia. Am J Physiol Lung Cell Mol Physiol 292: L678-L684, 2007.
20. Guilluy C, Sauzeau V, Rolli-Derkinderen M, Guerin P, Sagan C, Pacaud P, Loirand G. Inhibition of RhoA/Rho kinase pathway is involved in the beneficial effect of sildenafil on pulmonary hypertension. Br J Pharmacol 146: 1010-1018, 2005.
21. Hampl V, Herget J. Perinatal hypoxia increases hypoxic pulmonary vasoconstriction in adult rats recovering from chronic exposure to hypoxia. Am Rev Respir Dis 142: 619-624, 1990.
22. Hartshorne DJ. Myosin phosphatase: subunits and interactions. Acta Physiol Scand 164: 483-493, 1998.
23. Hemnes AR, Zaiman A, Champion HC. PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation. Am J Physiol Lung Cell Mol Physiol 294: L24-L33, 2008.
24. Hoskote A, Li J, Hickey C, Erickson S, Van Arsdell G, Stephens D, Holtby H, Bohn D, Adatia I. The effects of carbon dioxide on oxygenation and systemic, cerebral, and pulmonary vascular hemodynamics after the bidirectional superior cavopulmonary anastomosis. J Am Coll Cardiol 44: 1501-1509, 2004.
25. Howell K, Preston RJ, McLoughlin P. Chronic hypoxia causes angio-genesis in addition to remodelling in the adult rat pulmonary circulation. J Physiol 547: 133-145, 2003.
26. Jankov RP, Kantores C, Belcastro R, Yi M, Tanswell AK. Endothelin-1 inhibits apoptosis of pulmonary arterial smooth muscle in the neonatal rat. Pediatr Res 60: 245-251, 2006.
27. Jankov RP, Kantores C, Belcastro R, Yi S, Ridsdale RA, Post M, Tanswell AK. A role for platelet-derived growth factor fj-receptor in a newborn rat model of endothelin-mediated pulmonary vascular remodeling. Am J Physiol Lung Cell Mol Physiol 288: L1162-L1170, 2005.
28. Jankov RP, Kantores C, Pan J, Belik J. Contribution of xanthine oxidase-derived superoxide to chronic hypoxic pulmonary hypertension in neonatal rats. Am J Physiol Lung Cell Mol Physiol 294: L233-L245, 2008.
29. Jankov RP, Lewis P, Kantores C, Ivanovska J, Xu EZ, Van Vliet T, Lee AH, Tanswell AK, McNamara PJ. Peroxynitrite mediates right-ventricular dysfunction in nitric oxide-exposed juvenile rats. Free Radic Biol Med 49: 1453-1467, 2010.
30. Jankov RP, Tanswell AK. Hypercapnia and the neonate. Acta Paediatr 97: 1502-1509, 2008.
31. 2+ desensitization in pulmonary vascular smooth muscle through inhibition of RhoA/Rho kinase signaling. Am J Physiol Lung Cell Mol Physiol 287: L1220-L1229, 2004.
32. Kaiser JR, Gauss CH, Williams DK. The effects of hypercapnia on cerebral autoregulation in ventilated very low birth weight infants. Pediatr Res 58: 931-935, 2005.
33. Kantores C, McNamara PJ, Teixeira L, Engelberts D, Murthy P, Kavanagh BP, Jankov RP. Therapeutic hypercapnia prevents chronic hypoxia-induced pulmonary hypertension in the newborn rat. Am J Physiol Lung Cell Mol Physiol 291: L912-L922, 2006.
34. Kinoshita E, Kinoshita-Kikuta E, Takiyama K, Koike T. Phosphate-binding tag, a new tool to visualize phosphorylated proteins. Mol Cell Proteomics 5: 749-757, 2006.
35. Laffey JG, Engelberts D, Kavanagh BP. Buffering hypercapnic acidosis worsens acute lung injury. Am J Respir Crit Care Med 161: 141-146, 2000.
36. Laffey JG, Tanaka M, Engelberts D, Luo X, Yuan S, Tanswell AK, Post M, Lindsay T, Kavanagh BP. Therapeutic hypercapnia reduces pulmonary and systemic injury following in vivo lung reperfusion. Am J Respir Crit Care Med 162: 2287-2294, 2000.
37. Li J, Hoskote A, Hickey C, Stephens D, Bohn D, Holtby H, Van Arsdell G, Redington AN, Adatia I. Effect of carbon dioxide on systemic oxygenation, oxygen consumption, and blood lactate levels after bidirectional superior cavopulmonary anastomosis. Crit Care Med 33: 984-989, 2005.
38. Luo C, Ramachandran D, Ware DL, Ma TS, Clark JW. Modeling left ventricular diastolic dysfunction: classification and key indicators (Abstract). Theor Biol Med Model 8: 14, 2011.
39. Masood A, Yi M, Lau M, Belcastro R, Shek S, Pan J, Kantores C, McNamara PJ, Kavanagh BP, Belik J, Jankov RP, Tanswell AK. Therapeutic effects of hypercapnia on chronic lung injury and vascular remodeling in neonatal rats. Am J Physiol Lung Cell Mol Physiol 297: L920-L930, 2009.
40. Matsui T, Amano M, Yamamoto T, Chihara K, Nakafuku M, Ito M, Nakano T, Okawa K, Iwamatsu A, Kaibuchi K. Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. EMBO J 15: 2208-2216, 1996.
41. McNamara PJ, Murthy P, Kantores C, Teixeira L, Engelberts D, van Vliet T, Kavanagh BP, Jankov RP. Acute vasodilator effects of Rho-kinase inhibitors in neonatal rats with pulmonary hypertension unresponsive to nitric oxide. Am J Physiol Lung Cell Mol Physiol 294: L205-L213, 2008.
42. Ming XF, Viswambharan H, Barandier C, Ruffieux J, Kaibuchi K, Rusconi S, Yang Z. Rho GTPase/Rho kinase negatively regulates endothelial nitric oxide synthase phosphorylation through the inhibition of protein kinase B/Akt in human endothelial cells. Mol Cell Biol 22: 8467-8477, 2002.
43. Mohseni-Bod H, Bohn D. Pulmonary hypertension in congenital diaphragmatic hernia. Semin Pediatr Surg 16: 126-133, 2007.
44. Mortola JP, Morgan CA, Virgona V. Respiratory adaptation to chronic hypoxia in newborn rats. J Appl Physiol 61: 1329-1336, 1986.
45. Murata T, Sato K, Hori M, Ozaki H, Karaki H. Decreased endothelial nitric-oxide synthase (eNOS) activity resulting from abnormal interaction between eNOS and its regulatory proteins in hypoxia-induced pulmonary hypertension. J Biol Chem 277: 44085-44092, 2002.
46. Murphy JD, Rabinovitch M, Goldstein JD, Reid LM. The structural basis of persistent pulmonary hypertension of the newborn infant. J Pediatr 98: 962-967, 1981.
47. Murthy KS, Zhou H, Grider JR, Makhlouf GM. Inhibition of sustained smooth muscle contraction by PKA and PKG preferentially mediated by phosphorylation of RhoA. Am J Physiol Gastrointest Liver Physiol 284: G1006-G1016, 2003.
48. Nakaki T, Nakayama M, Kato R. Inhibition by nitric oxide and nitric oxide-producing vasodilators of DNA synthesis in vascular smooth muscle cells. Eur J Pharmacol 189: 347-353, 1990.
49. Nichol AD, O'Cronin DF, Naughton F, Hopkins N, Boylan J, McLoughlin P. Hypercapnic acidosis reduces oxidative reactions in endotoxin-induced lung injury. Anesthesiology 113: 116-125, 2010.
50. Ooi H, Cadogan E, Sweeney M, Howell K, O'Regan RG, McLoughlin P. Chronic hypercapnia inhibits hypoxic pulmonary vascular remodeling. Am J Physiol Heart Circ Physiol 278: H331-H338, 2000.
51. Parker TA, Abman SH. The pulmonary circulation in bronchopulmonary dysplasia. Semin Neonatol 8: 51-61, 2003.
52. Rabinovitch M. Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest 118: 2372-2379, 2008.
53. Satoh K, Fukumoto Y, Shimokawa H. Rho-kinase: important new therapeutic target in cardiovascular diseases. Am J Physiol Heart Circ Physiol 301: H287-H296, 2011.
54. 2+ sensitization of contraction in vascular smooth muscle. J Biol Chem 275: 21722-21729, 2000.
55. Sawada N, Itoh H, Yamashita J, Doi K, Inoue M, Masatsugu K, Fukunaga Y, Sakaguchi S, Sone M, Yamahara K, Yurugi T, Nakao K. cGMP-dependent protein kinase phosphorylates and inactivates RhoA. Biochem Biophys Res Commun 280: 798-805, 2001.
56. Schaefer A, Meyer GP, Brand B, Hilfiker-Kleiner D, Drexler H, Klein G. Effects of anesthesia on diastolic function in mice assessed by echocardiography. Echocardiography 22: 665-670, 2005.
57. Shibata K, Cregg N, Engelberts D, Takeuchi A, Fedorko L, Kavanagh BP. Hypercapnic acidosis may attenuate acute lung injury by inhibition of endogenous xanthine oxidase. Am J Respir Crit Care Med 158: 1578-1584, 1998.
58. Shimokawa H. Rho-kinase as a novel therapeutic target in treatment of cardiovascular diseases. J Cardiovasc Pharmacol 39: 319-327, 2002.
59. 2+ sensitivity of smooth muscle and non-muscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 83: 1325-1358, 2003.
60. Somlyo AP, Somlyo AV. Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J Physiol 522: 177-185, 2000.
61. Sterni LM, Bamford OS, Wasicko MJ, Carroll JL. Chronic hypoxia abolished the postnatal increase in carotid body type I cell sensitivity to hypoxia. Am J Physiol Lung Cell Mol Physiol 277: L645-L652, 1999.
62. Swenson ER, Robertson HT, Hlastala MP. Effects of inspired carbon dioxide on ventilation-perfusion matching in normoxia, hypoxia, and hyperoxia. Am J Respir Crit Care Med 149: 1563-1569, 1994.
63. Takeshita K, Suzuki Y, Nishio K, Takeuchi O, Toda K, Kudo H, Miyao N, Ishii M, Sato N, Naoki K, Aoki T, Suzuki K, Hiraoka R, Yamaguchi K. Hypercapnic acidosis attenuates endotoxin-induced nuclear factor-kB activation. Am J Respir Cell Mol Biol 29: 124-132, 2003.
64. Thibeault DW, Truog WE, Ekekezie II. Acinar arterial changes with chronic lung disease of prematurity in the surfactant era. Pediatr Pulmonol 36: 482-489, 2003.
65. Thomae KR, Nakayama DK, Billiar TR, Simmons RL, Pitt BR, Davies P. The effect of nitric oxide on fetal pulmonary artery smooth muscle growth. J Surg Res 59: 337-343, 1995.
66. van Loon RL, Roofthooft MT, Delhaas T, van Osch-Gevers M, Ten Harkel AD, Strengers JL, Backx A, Hillege HL, Berger RM. Outcome of pediatric patients with pulmonary arterial hypertension in the era of new medical therapies. Am J Cardiol 106: 117-124, 2010.
67. Viles PH, Shepherd JT. Evidence for a dilator action of carbon dioxide on the pulmonary vessels of the cat. Circ Res 22: 325-332, 1968.
68. Walley KR, Lewis TH, Wood LD. Acute respiratory acidosis decreases left ventricular contractility but increases cardiac output in dogs. Circ Res 67: 628-635, 1990.
69. Weber T, Tschernich H, Sitzwohl C, Ullrich R, Germann P, Zimpfer M, Sladen RN, Huemer G. Tromethamine buffer modifies the depressant effect of permissive hypercapnia on myocardial contractility in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 162: 1361-1365, 2000.
70. Wexels JC, Mjos OD. Effects of carbon dioxide and pH on myocardial function in dogs with acute left ventricular failure. Crit Care Med 15: 1116-1120, 1987.
71. Wexels JC, Myhre ES, Mjos OD. Effects of hypo- and hyper-capnia on myocardial blood flow and metabolism during epinephrine infusion in the dog. Can J Physiol Pharmacol 64: 44-49, 1986.
72. Wilson RM, De Silva DS, Sato K, Izumiya Y, Sam F. Effects of fixed-dose isosorbide dinitrate/hydralazine on diastolic function and exercise capacity in hypertension-induced diastolic heart failure. Hypertension 54: 583-590, 2009.
73. Wooldridge AA, MacDonald JA, Erdodi F, Ma C, Borman MA, Hartshorne DJ, Haystead TA. Smooth muscle phosphatase is regulated in vivo by exclusion of phosphorylation of threonine 696 of MYPT1 by phosphorylation of Serine 695 in response to cyclic nucleotides. J Biol Chem 279: 34496-34504, 2004.
74. Xu EZ, Kantores C, Ivanovska J, Engelberts D, Kavanagh BP, McNamara PJ, Jankov RP. Rescue treatment with a Rho-kinase inhibitor normalizes right ventricular function and reverses remodeling in juvenile rats with chronic pulmonary hypertension. Am J Physiol Heart Circ Physiol 299: H1854-H1864, 2010.
75. Ziino AJ, Ivanovska J, Belcastro R, Kantores C, Xu EZ, Lau M, McNamara PJ, Tanswell AK, Jankov RP. Effects of Rho-kinase inhibition on pulmonary hypertension, lung growth, and structure in neonatal rats chronically exposed to hypoxia. Pediatr Res 67: 177-182, 2010.