| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
CALL FOR PAPERS
Rho GTPases in Lung Physiology and Disease
1Cardiovascular Pulmonary Research Laboratory and 2Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado 80262
Submitted 1 April 2003 ; accepted in final form 13 February 2004
RhoA GTPase mediates a variety of cellular responses, including activation of the contractile apparatus, growth, and gene expression. Acute hypoxia activates RhoA and, in turn, its downstream effector, Rho-kinase, and previous studies in rats have suggested a role for Rho/Rho-kinase signaling in both acute and chronically hypoxic pulmonary vasoconstriction. We therefore hypothesized that activation of Rho/Rho-kinase in the pulmonary circulation of mice contributes to acute hypoxic pulmonary vasoconstriction and chronic hypoxia-induced pulmonary hypertension and vascular remodeling. In isolated, salt solution-perfused mouse lungs, acute administration of the Rho-kinase inhibitor Y-27632 (1 x 10–5 M) attenuated hypoxic vasoconstriction as well as that due to angiotensin II and KCl. Chronic treatment with Y-27632 (30 mg·kg–1·day–1) via subcutaneous osmotic pump decreased right ventricular systolic pressure, right ventricular hypertrophy, and neomuscularization of the distal pulmonary vasculature in mice exposed to hypobaric hypoxia for 14 days. Analysis of a small number of proximal pulmonary arteries suggested that Y-27632 treatment reduced the level of phospho-CPI-17, a Rho-kinase target, in hypoxic lungs. We also found that endothelial nitric oxide synthase protein in hypoxic lungs was augmented by Y-27632, suggesting that enhanced nitric oxide production might have played a role in the Y-27632-induced attenuation of chronically hypoxic pulmonary hypertension. In conclusion, Rho/Rho-kinase activation is important in the effects of both acute and chronic hypoxia on the pulmonary circulation of mice, possibly by contributing to both vasoconstriction and vascular remodeling.
RhoA; Y-27632
This article has been cited by other articles:
|
|
 |
|
  N. Homma, T. Nagaoka, V. Karoor, M. Imamura, L. Taraseviciene-Stewart, L. A. Walker, K. A. Fagan, I. F. McMurtry, and M. Oka Involvement of RhoA/Rho kinase signaling in protection against monocrotaline-induced pulmonary hypertension in pneumonectomized rats by dehydroepiandrosterone Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L71 - L78. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. S. Broughton, B. R. Walker, and T. C. Resta Chronic hypoxia induces Rho kinase-dependent myogenic tone in small pulmonary arteries Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L797 - L806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Jakoubek, J. Bibova, J. Herget, and V. Hampl Chronic hypoxia increases fetoplacental vascular resistance and vasoconstrictor reactivity in the rat Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1638 - H1644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. McNamara, P. Murthy, C. Kantores, L. Teixeira, D. Engelberts, T. van Vliet, B. P. Kavanagh, and R. P. Jankov Acute vasodilator effects of Rho-kinase inhibitors in neonatal rats with pulmonary hypertension unresponsive to nitric oxide Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L205 - L213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Dhaliwal, D. B. Casey, A. J. Greco, A. M. Badejo Jr., T. B. Gallen, S. N. Murthy, B. D. Nossaman, A. L. Hyman, and P. J. Kadowitz Rho kinase and Ca2+ entry mediate increased pulmonary and systemic vascular resistance in L-NAME-treated rats Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1306 - L1313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Carlin, A. J. Peacock, and D. J. Welsh Fluvastatin Inhibits Hypoxic Proliferation and p38 MAPK Activity in Pulmonary Artery Fibroblasts Am. J. Respir. Cell Mol. Biol., October 1, 2007; 37(4): 447 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, L. Weigand, J. Foxson, L. A. Shimoda, and J. T. Sylvester Ca2+ signaling in hypoxic pulmonary vasoconstriction: effects of myosin light chain and Rho kinase antagonists Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L674 - L685. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Vermeersch, E. Buys, P. Pokreisz, G. Marsboom, F. Ichinose, P. Sips, M. Pellens, H. Gillijns, M. Swinnen, A. Graveline, et al. Soluble Guanylate Cyclase-{alpha}1 Deficiency Selectively Inhibits the Pulmonary Vasodilator Response to Nitric Oxide and Increases the Pulmonary Vascular Remodeling Response to Chronic Hypoxia Circulation, August 21, 2007; 116(8): 936 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Barman Vasoconstrictor effect of endothelin-1 on hypertensive pulmonary arterial smooth muscle involves Rho-kinase and protein kinase C Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L472 - L479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Herrera, V. M. Pulgar, R. A. Riquelme, E. M. Sanhueza, R. V. Reyes, G. Ebensperger, J. T. Parer, E. A. Valdez, D. A. Giussani, C. E. Blanco, et al. High-altitude chronic hypoxia during gestation and after birth modifies cardiovascular responses in newborn sheep Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2234 - R2240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Oka, V. Karoor, N. Homma, T. Nagaoka, E. Sakao, S. M. Golembeski, J. Limbird, M. Imamura, S. A. Gebb, K. A. Fagan, et al. Dehydroepiandrosterone upregulates soluble guanylate cyclase and inhibits hypoxic pulmonary hypertension Cardiovasc Res, June 1, 2007; 74(3): 377 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. de Frutos, R. Spangler, D. Alo, and L. V. G. Bosc NFATc3 Mediates Chronic Hypoxia-induced Pulmonary Arterial Remodeling with {alpha}-Actin Up-regulation J. Biol. Chem., May 18, 2007; 282(20): 15081 - 15089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Y. Rochefort and E. D. Michelakis COUNTERPOINT: RELEASE OF AN ENDOTHELIUM-DERIVED VASOCONSTRICTOR AND RHOA/RHO KINASE-MEDIATED CALCIUM SENSITIZATION OF SMOOTH MUSCLE CELL CONTRACTION ARE NOT THE MAIN EFFECTORS FOR FULL AND SUSTAINED HPV J Appl Physiol, May 1, 2007; 102(5): 2072 - 2075. [Full Text] [PDF]
|
|
|
|
|
|
T. P. Robertson Point: Release of an endothelium-derived vasoconstrictor and RhoA/Rho kinase-mediated calcium sensitization of smooth muscle cell contraction are/are not the main effectors for full and sustained hypoxic pulmonary vasoconstriction J Appl Physiol, May 1, 2007; 102(5): 2071 - 2072. [Full Text] [PDF]
|
|
|
|
|
|
R. E. Girgis, S. Mozammel, H. C. Champion, D. Li, X. Peng, L. Shimoda, R. M. Tuder, R. A. Johns, and P. M. Hassoun Regression of chronic hypoxic pulmonary hypertension by simvastatin Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1105 - L1110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Crossno Jr., C. V. Garat, J. E. B. Reusch, K. G. Morris, E. C. Dempsey, I. F. McMurtry, K. R. Stenmark, and D. J. Klemm Rosiglitazone attenuates hypoxia-induced pulmonary arterial remodeling Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L885 - L897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Oka, N. Homma, L. Taraseviciene-Stewart, K. G. Morris, D. Kraskauskas, N. Burns, N. F. Voelkel, and I. F. McMurtry Rho Kinase-Mediated Vasoconstriction Is Important in Severe Occlusive Pulmonary Arterial Hypertension in Rats Circ. Res., March 30, 2007; 100(6): 923 - 929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Gao, A. D. Portugal, S. Negash, W. Zhou, L. D. Longo, and J. Usha Raj 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, March 1, 2007; 292(3): L678 - L684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Parker, G. Roe, T. R. Grover, and S. H. Abman Rho kinase activation maintains high pulmonary vascular resistance in the ovine fetal lung Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L976 - L982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Stenmark, K. A. Fagan, and M. G. Frid Hypoxia-Induced Pulmonary Vascular Remodeling: Cellular and Molecular Mechanisms Circ. Res., September 29, 2006; 99(7): 675 - 691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nagaoka, S. A. Gebb, V. Karoor, N. Homma, K. G. Morris, I. F. McMurtry, and M. Oka Involvement of RhoA/Rho kinase signaling in pulmonary hypertension of the fawn-hooded rat J Appl Physiol, March 1, 2006; 100(3): 996 - 1002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Loirand, P. Guerin, and P. Pacaud Rho Kinases in Cardiovascular Physiology and Pathophysiology Circ. Res., February 17, 2006; 98(3): 322 - 334. [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]
|
|
|
|
|
|
J. Q. Liu, I. N. Zelko, E. M. Erbynn, J. S. K. Sham, and R. J. Folz Hypoxic pulmonary hypertension: role of superoxide and NADPH oxidase (gp91phox) Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L2 - L10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Naik, L. Xiang, and R. L. Hester Enhanced role for RhoA-associated kinase in adrenergic-mediated vasoconstriction in gracilis arteries from obese Zucker rats Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R154 - R161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. K. Weir, J. Lopez-Barneo, K. J. Buckler, and S. L. Archer Acute Oxygen-Sensing Mechanisms. N. Engl. J. Med., November 10, 2005; 353(19): 2042 - 2055. [Full Text] [PDF]
|
|
|
|
|
|
J. L. Losapio, R. S. Sprague, A. J. Lonigro, and A. H. Stephenson 5,6-EET-induced contraction of intralobar pulmonary arteries depends on the activation of Rho-kinase J Appl Physiol, October 1, 2005; 99(4): 1391 - 1396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Stenmark and I. F. McMurtry Vascular Remodeling Versus Vasoconstriction in Chronic Hypoxic Pulmonary Hypertension: A Time for Reappraisal? Circ. Res., July 22, 2005; 97(2): 95 - 98. [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Hyvelin, K. Howell, A. Nichol, C. M. Costello, R. J. Preston, and P. McLoughlin Inhibition of Rho-Kinase Attenuates Hypoxia-Induced Angiogenesis in the Pulmonary Circulation Circ. Res., July 22, 2005; 97(2): 185 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Weigand, J. Foxson, J. Wang, L. A. Shimoda, and J. T. Sylvester Inhibition of hypoxic pulmonary vasoconstriction by antagonists of store-operated Ca2+ and nonselective cation channels Am J Physiol Lung Cell Mol Physiol, July 1, 2005; 289(1): L5 - L13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Rhodes Comparative physiology of hypoxic pulmonary hypertension: historical clues from brisket disease J Appl Physiol, March 1, 2005; 98(3): 1092 - 1100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Naik, S. Earley, T. C. Resta, and B. R. Walker Pressure-induced smooth muscle cell depolarization in pulmonary arteries from control and chronically hypoxic rats does not cause myogenic vasoconstriction J Appl Physiol, March 1, 2005; 98(3): 1119 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nagaoka, K. A. Fagan, S. A. Gebb, K. G. Morris, T. Suzuki, H. Shimokawa, I. F. McMurtry, and M. Oka Inhaled Rho Kinase Inhibitors Are Potent and Selective Vasodilators in Rat Pulmonary Hypertension Am. J. Respir. Crit. Care Med., March 1, 2005; 171(5): 494 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. B. Waypa and P. T. Schumacker Hypoxic pulmonary vasoconstriction: redox events in oxygen sensing J Appl Physiol, January 1, 2005; 98(1): 404 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Jernigan, B. R. Walker, and T. C. Resta Chronic hypoxia augments protein kinase G-mediated Ca2+ desensitization in pulmonary vascular smooth muscle through inhibition of RhoA/Rho kinase signaling Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1220 - L1229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Sylvester The tone of pulmonary smooth muscle: ROK and Rho music? Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L624 - L630. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
