|
|
||||||||
Journal of Applied Physiology, Vol 79, Issue 6 2122-2131, Copyright © 1995 by American Physiological Society
ARTICLES |
S. J. Chen, Y. F. Chen, Q. C. Meng, J. Durand, V. S. Dicarlo and S. Oparil
Division of Cardiovascular Disease, University of Alabama at Birmingham 35294, USA.
The current study examined the effects of bosentan, an orally active antagonist of endothelin-A and -B receptors, on the development and maintenance of hypoxia (10% O2)-induced pulmonary hypertension and vascular remodeling in the rat. Pretreatment with bosentan (100 mg.kg-1.day-1, 1 gavage/day for 2 days) completely blocked the pulmonary vasoconstrictor response to acute hypoxia. Chronic bosentan treatment (100 mg.kg-1.day-1 po in the food) instituted 48 h before hypoxic exposure prevented the subsequent development of pulmonary hypertension, attenuated the associated right heart hypertrophy, and prevented the remodeling of small (50-100 microns) pulmonary arteries without altering systemic arterial pressure. Institution of bosentan treatment (for 4 wk) after 2 wk of hypoxia produced a significant reversal of established hypoxia-induced pulmonary hypertension (from 36 +/- 1 to 25 +/- 1 mmHg), right heart hypertrophy, and pulmonary vascular remodeling despite continuing hypoxic exposure. These findings support the hypothesis that endogenous endothelin-1 plays a major role in hypoxic pulmonary vasoconstriction and/or hypertension, right heart hypertrophy, and pulmonary vascular remodeling and suggest that endothelin-receptor blockade may be useful in the treatment of hypoxic pulmonary hypertension humans.
This article has been cited by other articles:
![]() |
V. Faoro, S. Boldingh, M. Moreels, S. Martinez, M. Lamotte, P. Unger, S. Brimioulle, S. Huez, and R. Naeije Bosentan Decreases Pulmonary Vascular Resistance and Improves Exercise Capacity in Acute Hypoxia Chest, May 1, 2009; 135(5): 1215 - 1222. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. P. Talbot, G. M. Balanos, P. A. Robbins, and K. L. Dorrington Can intravenous endothelin-1 be used to enhance hypoxic pulmonary vasoconstriction in healthy humans? Br. J. Anaesth., October 1, 2008; 101(4): 466 - 472. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. F. Opitz, R. Ewert, W. Kirch, and D. Pittrow Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter? Eur. Heart J., August 2, 2008; 29(16): 1936 - 1948. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. O. Schwenke, T. Tokudome, M. Shirai, H. Hosoda, T. Horio, I. Kishimoto, and K. Kangawa Exogenous Ghrelin Attenuates the Progression of Chronic Hypoxia-Induced Pulmonary Hypertension in Conscious Rats Endocrinology, January 1, 2008; 149(1): 237 - 244. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. E. King Jr., J. Behr, K. K. Brown, R. M. du Bois, L. Lancaster, J. A. de Andrade, G. Stahler, I. Leconte, S. Roux, and G. Raghu BUILD-1: A Randomized Placebo-controlled Trial of Bosentan in Idiopathic Pulmonary Fibrosis Am. J. Respir. Crit. Care Med., January 1, 2008; 177(1): 75 - 81. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Dupuis Endothelin: setting the scene in PAH Eur. Respir. Rev., August 1, 2007; 16(102): 3 - 7. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Chen, L. He, X. Liu, B. Dinger, L. Stensaas, and S. Fidone Effect of the endothelin receptor antagonist bosentan on chronic hypoxia-induced morphological and physiological changes in rat carotid body Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1257 - L1262. [Abstract] [Full Text] [PDF] |
||||
![]() |
M D'Alto, C D Vizza, E Romeo, R Badagliacca, G Santoro, R Poscia, B Sarubbi, M Mancone, P Argiento, F Ferrante, et al. Long term effects of bosentan treatment in adult patients with pulmonary arterial hypertension related to congenital heart disease (Eisenmenger physiology): safety, tolerability, clinical, and haemodynamic effect Heart, May 1, 2007; 93(5): 621 - 625. [Abstract] [Full Text] [PDF] |
||||
![]() |
S Maiya, A A Hislop, Y Flynn, and S G Haworth Response to bosentan in children with pulmonary hypertension Heart, May 1, 2006; 92(5): 664 - 670. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Weigand, J. T. Sylvester, and L. A. Shimoda Mechanisms of endothelin-1-induced contraction in pulmonary arteries from chronically hypoxic rats Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L284 - L290. [Abstract] [Full Text] [PDF] |
||||
![]() |
S C Apostolopoulou, A Manginas, D V Cokkinos, and S Rammos Effect of the oral endothelin antagonist bosentan on the clinical, exercise, and haemodynamic status of patients with pulmonary arterial hypertension related to congenital heart disease Heart, November 1, 2005; 91(11): 1447 - 1452. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Henriques-Coelho, J. Correia-Pinto, R. Roncon-Albuquerque Jr, M. J. Baptista, A. P. Lourenco, S. M. Oliveira, A. Brandao-Nogueira, A. Teles, J. M. Fortunato, and A. F. Leite-Moreira Endogenous production of ghrelin and beneficial effects of its exogenous administration in monocrotaline-induced pulmonary hypertension Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2885 - H2890. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Li, S. Oparil, W. Feng, and Y.-F. Chen Hypoxia-responsive growth factors upregulate periostin and osteopontin expression via distinct signaling pathways in rat pulmonary arterial smooth muscle cells J Appl Physiol, October 1, 2004; 97(4): 1550 - 1558. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Suleman and A. E. Frost Transition From Epoprostenol and Treprostinil to the Oral Endothelin Receptor Antagonist Bosentan in Patients With Pulmonary Hypertension Chest, September 1, 2004; 126(3): 808 - 815. [Abstract] [Full Text] [PDF] |
||||
![]() |
E Hachulla and J G Coghlan A new era in the management of pulmonary arterial hypertension related to scleroderma: endothelin receptor antagonism Ann Rheum Dis, September 1, 2004; 63(9): 1009 - 1014. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. M. Tsai, M. Wang, M. W. Turrentine, Y. Mahomed, J. W. Brown, and D. R. Meldrum Hypoxic pulmonary vasoconstriction in cardiothoracic surgery: basic mechanisms to potential therapies Ann. Thorac. Surg., July 1, 2004; 78(1): 360 - 368. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. B. Badesch, S. H. Abman, G. S. Ahearn, R. J. Barst, D. C. McCrory, G. Simonneau, and V. V. McLaughlin Medical Therapy For Pulmonary Arterial Hypertension: ACCP Evidence-Based Clinical Practice Guidelines Chest, July 1, 2004; 126(1_suppl): 35S - 62S. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Abraham, K. Krenn, G. Seebacher, P. Paulus, W. Klepetko, and S. Aharinejad Upregulated hypoxia-inducible factor-1 DNA binding activity to the vascular endothelial growth factor-A promoter mediates increased vascular permeability in donor lung grafts Ann. Thorac. Surg., May 1, 2004; 77(5): 1751 - 1755. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. L. Semenza O2-regulated gene expression: transcriptional control of cardiorespiratory physiology by HIF-1 J Appl Physiol, March 1, 2004; 96(3): 1173 - 1177. [Abstract] [Full Text] [PDF] |
||||
![]() |
S C Apostolopoulou, S Rammos, Z S Kyriakides, D J Webb, N R Johnston, D V Cokkinos, and D T. Kremastinos Acute endothelin A receptor antagonism improves pulmonary and systemic haemodynamics in patients with pulmonary arterial hypertension that is primary or autoimmune and related to congenital heart disease Heart, October 1, 2003; 89(10): 1221 - 1226. [Abstract] [Full Text] [PDF] |
||||
![]() |
W.-M. Zhang, K.-P. Yip, M.-J. Lin, L. A. Shimoda, W.-H. Li, and J. S. K. Sham ET-1 activates Ca2+ sparks in PASMC: local Ca2+ signaling between inositol trisphosphate and ryanodine receptors Am J Physiol Lung Cell Mol Physiol, September 1, 2003; 285(3): L680 - L690. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Sharma Treatment of Pulmonary Arterial Hypertension: A Step Forward Chest, July 1, 2003; 124(1): 8 - 11. [Full Text] [PDF] |
||||
![]() |
O. Sitbon, D. B. Badesch, R. N. Channick, A. Frost, I. M. Robbins, G. Simonneau, V. F. Tapson, and L. J. Rubin Effects of the Dual Endothelin Receptor Antagonist Bosentan in Patients With Pulmonary Arterial Hypertension: A 1-Year Follow-up Study Chest, July 1, 2003; 124(1): 247 - 254. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. W Kenyon and J. M Nappi Bosentan for the Treatment of Pulmonary Arterial Hypertension Ann. Pharmacother., July 1, 2003; 37(7): 1055 - 1062. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Hubloue, D. Biarent, S. A. Kafi, G. Bejjani, F. Kerbaul, R. Naeije, and M. Leeman Endogenous endothelins and nitric oxide in hypoxic pulmonary vasoconstriction Eur. Respir. J., January 1, 2003; 21(1): 19 - 24. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. V. Remillard, W.-M. Zhang, L. A. Shimoda, and J. S. K. Sham Physiological properties and functions of Ca2+ sparks in rat intrapulmonary arterial smooth muscle cells Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L433 - L444. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Chen, L. He, B. Dinger, L. Stensaas, and S. Fidone Role of endothelin and endothelin A-type receptor in adaptation of the carotid body to chronic hypoxia Am J Physiol Lung Cell Mol Physiol, June 1, 2002; 282(6): L1314 - L1323. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. J. Rubin, D. B. Badesch, R. J. Barst, N. Galie, C. M. Black, A. Keogh, T. Pulido, A. Frost, S. Roux, I. Leconte, et al. Bosentan Therapy for Pulmonary Arterial Hypertension N. Engl. J. Med., March 21, 2002; 346(12): 896 - 903. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. H.S. Kim and L. J. Rubin Endothelin in Health and Disease: Endothelin Receptor Antagonists in the Management of Pulmonary Artery Hypertension Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2002; 7(1): 9 - 19. [Abstract] [PDF] |
||||
![]() |
F. Brunner, G. Wolkart, and S. Haleen Defective Intracellular Calcium Handling in Monocrotaline-Induced Right Ventricular Hypertrophy: Protective Effect of Long-Term Endothelin-A Receptor Blockade with 2-Benzo[1,3]dioxol-5-yl-3-benzyl-4-(4-methoxy-phenyl-)- 4-oxobut-2-enoate-sodium (PD 155080) J. Pharmacol. Exp. Ther., February 1, 2002; 300(2): 442 - 449. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. DAVIE, S. J. HALEEN, P. D. UPTON, J. M. POLAK, M. H. YACOUB, N. W. MORRELL, and J. WHARTON ETA and ETB Receptors Modulate the Proliferation of Human Pulmonary Artery Smooth Muscle Cells Am. J. Respir. Crit. Care Med., February 1, 2002; 165(3): 398 - 405. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. A. Shimoda, J. T. Sylvester, G. M. Booth, T. H. Shimoda, S. Meeker, B. J. Undem, and J. S. K. Sham Inhibition of voltage-gated K+ currents by endothelin-1 in human pulmonary arterial myocytes Am J Physiol Lung Cell Mol Physiol, November 1, 2001; 281(5): L1115 - L1122. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Takahashi, S. Soma, M. Muramatsu, M. Oka, and Y. Fukuchi Upregulation of ET-1 and its receptors and remodeling in small pulmonary veins under hypoxic conditions Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1104 - L1114. [Abstract] [Full Text] [PDF] |
||||
![]() |
Q. Liu, J. S. K. Sham, L. A. Shimoda, and J. T. Sylvester Hypoxic constriction of porcine distal pulmonary arteries: endothelium and endothelin dependence Am J Physiol Lung Cell Mol Physiol, May 1, 2001; 280(5): L856 - L865. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. D. Ivy, I. F. McMurtry, M. Yanagisawa, C. E. Gariepy, T. D. Le Cras, S. A. Gebb, K. G. Morris, R. C. Wiseman, and S. H. Abman Endothelin B receptor deficiency potentiates ET-1 and hypoxic pulmonary vasoconstriction Am J Physiol Lung Cell Mol Physiol, May 1, 2001; 280(5): L1040 - L1048. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. F. Luscher and M. Barton Endothelins and Endothelin Receptor Antagonists : Therapeutic Considerations for a Novel Class of Cardiovascular Drugs Circulation, November 7, 2000; 102(19): 2434 - 2440. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. A. Shimoda, J. S. K. Sham, T. H. Shimoda, and J. T. Sylvester L-type Ca2+ channels, resting [Ca2+]i, and ET-1-induced responses in chronically hypoxic pulmonary myocytes Am J Physiol Lung Cell Mol Physiol, November 1, 2000; 279(5): L884 - L894. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. C. Carpenter and K. R. Stenmark Endothelin receptor blockade decreases lung water in young rats exposed to viral infection and hypoxia Am J Physiol Lung Cell Mol Physiol, September 1, 2000; 279(3): L547 - L554. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. S. K. Sham, B. R. Crenshaw Jr., L.-H. Deng, L. A. Shimoda, and J. T. Sylvester Effects of hypoxia in porcine pulmonary arterial myocytes: roles of KV channel and endothelin-1 Am J Physiol Lung Cell Mol Physiol, August 1, 2000; 279(2): L262 - L272. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J. Williamson, L. L. Wallman, R. Jones, A. M. Keogh, F. Scroope, BEd, R. Penny, C. Weber, and P. S. Macdonald Hemodynamic Effects of Bosentan, an Endothelin Receptor Antagonist, in Patients With Pulmonary Hypertension Circulation, July 25, 2000; 102(4): 411 - 418. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Sato, Y. Morio, K. G. Morris, D. M. Rodman, and I. F. McMurtry Mechanism of hypoxic pulmonary vasoconstriction involves ETA receptor-mediated inhibition of KATP channel Am J Physiol Lung Cell Mol Physiol, March 1, 2000; 278(3): L434 - L442. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Doi, N. Smedira, and P. A. Murray Pulmonary vasoregulation by endothelin in conscious dogs after left lung transplantation J Appl Physiol, January 1, 2000; 88(1): 210 - 218. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. A. Shimoda, J. T. Sylvester, and J. S. K. Sham Mobilization of intracellular Ca2+ by endothelin-1 in rat intrapulmonary arterial smooth muscle cells Am J Physiol Lung Cell Mol Physiol, January 1, 2000; 278(1): L157 - L164. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Pearl, S. A. Wellmann, J. L. McNamara, J. P. Lombardi, C. J. Wagner, J. L. Raake, and D. P. Nelson Bosentan prevents hypoxia-reoxygenation-induced pulmonary hypertension and improves pulmonary function Ann. Thorac. Surg., November 1, 1999; 68(5): 1714 - 1721. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. A. Shimoda, J. T. Sylvester, and J. S. K. Sham Chronic hypoxia alters effects of endothelin and angiotensin on K+ currents in pulmonary arterial myocytes Am J Physiol Lung Cell Mol Physiol, September 1, 1999; 277(3): L431 - L439. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Sartori, L. Vollenweider, B.-M. Loffler, A. Delabays, P. Nicod, P. Bartsch, and U. Scherrer Exaggerated Endothelin Release in High-Altitude Pulmonary Edema Circulation, May 25, 1999; 99(20): 2665 - 2668. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Muramatsu, M. Oka, Y. Morio, S. Soma, H. Takahashi, and Y. Fukuchi Chronic hypoxia augments endothelin-B receptor-mediated vasodilation in isolated perfused rat lungs Am J Physiol Lung Cell Mol Physiol, February 1, 1999; 276(2): L358 - L364. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Y. Yu, M. G. Frid, L. A. Shimoda, C. M. Wiener, K. Stenmark, and G. L. Semenza Temporal, spatial, and oxygen-regulated expression of hypoxia-inducible factor-1 in the lung Am J Physiol Lung Cell Mol Physiol, October 1, 1998; 275(4): L818 - L826. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Hoshino, R. Yamauchi, K. Kikkawa, H. Yabana, and S. Murata Pharmacological Profile of T-0201, a Highly Potent and Orally Active Endothelin Receptor Antagonist J. Pharmacol. Exp. Ther., August 1, 1998; 286(2): 643 - 649. [Abstract] [Full Text] |
||||
![]() |
L. A. Shimoda, J. T. Sylvester, and J. S. K. Sham Inhibition of voltage-gated K+ current in rat intrapulmonary arterial myocytes by endothelin-1 Am J Physiol Lung Cell Mol Physiol, May 1, 1998; 274(5): L842 - L853. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Dunbar Ivy, T. D. Le Cras, M. P. Horan, and S. H. Abman Increased lung preproET-1 and decreased ETB-receptor gene expression in fetal pulmonary hypertension Am J Physiol Lung Cell Mol Physiol, April 1, 1998; 274(4): L535 - L541. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. P. Gaine, M. A. Hales, and N. A. Flavahan Hypoxic pulmonary endothelial cells release a diffusible contractile factor distinct from endothelin Am J Physiol Lung Cell Mol Physiol, April 1, 1998; 274(4): L657 - L664. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. C. Underwood, S. Bochnowicz, R. R. Osborn, M. A. Luttmann, and D. W. P. Hay Nonpeptide Endothelin Receptor Antagonists. X. Inhibition of Endothelin-1- and Hypoxia-Induced Pulmonary Pressor Responses in the Guinea Pig by the Endothelin Receptor Antagonist, SB 217242 J. Pharmacol. Exp. Ther., December 1, 1997; 283(3): 1130 - 1137. [Abstract] [Full Text] |
||||
![]() |
J.-P. Gratton, G. Cournoyer, B.-M. Loffler, P. Sirois, and P. D'Orleans-Juste ETB Receptor and Nitric Oxide Synthase Blockade Induce BQ-123–Sensitive Pressor Effects in the Rabbit Hypertension, November 1, 1997; 30(5): 1204 - 1209. [Abstract] [Full Text] |
||||
![]() |
N. S. Hill, R. R. Warburton, L. Pietras, and J. R. Klinger Nonspecific endothelin-receptor antagonist blunts monocrotaline-induced pulmonary hypertension in rats J Appl Physiol, October 1, 1997; 83(4): 1209 - 1215. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. R. FISCHER, D. J. DEYO, H. G. BONE, R. MCGUIRE, L. D. TRABER, and D. L. TRABER Nitric Oxide Synthase Inhibition Restores Hypoxic Pulmonary Vasoconstriction in Sepsis Am. J. Respir. Crit. Care Med., September 1, 1997; 156(3): 833 - 839. [Abstract] [Full Text] [PDF] |
||||
![]() |
S.-H. PARK, D. SALEH, A. GIAID, and R. P. MICHEL Increased Endothelin-1 in Bleomycin-induced Pulmonary Fibrosis and the Effect of an Endothelin Receptor Antagonist Am. J. Respir. Crit. Care Med., July 1, 1997; 156(2): 600 - 608. [Abstract] [Full Text] |
||||
![]() |
D. D. Ivy, M. Yanagisawa, C. E. Gariepy, S. A. Gebb, K. L. Colvin, and I. F. McMurtry Exaggerated hypoxic pulmonary hypertension in endothelin B receptor-deficient rats Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L703 - L712. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |