HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 100/3/996    most recent 01028.2005v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (18) Citing Articles via Google Scholar Google Scholar Articles by Nagaoka, T. Articles by Oka, M. Search for Related Content PubMed PubMed Citation Articles by Nagaoka, T. Articles by Oka, M.

Involvement of RhoA/Rho kinase signaling in pulmonary hypertension of the fawn-hooded rat

Cardiovascular Pulmonary Research Laboratory, Department of Medicine, University of Colorado at Denver and Health Sciences Center, Denver, Colorado

Submitted 23 August 2005 ; accepted in final form 29 November 2005

The fawn-hooded rat (FHR) develops severe pulmonary hypertension (PH) when raised for the first 3–4 wk of life in the mild hypoxia of Denver’s altitude (5,280 ft.). The PH is associated with sustained pulmonary vasoconstriction and pulmonary artery remodeling. Furthermore, lung alveolarization and vascularization are reduced in the Denver FHR. We have recently shown that RhoA/Rho kinase signaling is involved in both vasoconstriction and vascular remodeling in animal models of hypoxic PH. In this study, we investigated the role of RhoA/Rho kinase signaling in the PH of Denver FHR. In -toxin permeabilized pulmonary arteries from Denver FHR, the contractile sensitivity to Ca²⁺ was increased compared with those from sea-level FHR. RhoA activity and Rho kinase I protein expression in pulmonary arteries of Denver FHR (10-wk-old) were higher than in those of sea-level FHR. Acute inhalation of the Rho kinase inhibitor fasudil selectively reduced the elevated pulmonary arterial pressure in Denver FHR in vivo. Chronic fasudil treatment (30 mg·kg^–1·day^–1, from birth to 10 wk old) markedly reduced the development of PH and improved lung alveolarization and vascularization in Denver FHR. These results suggest that Rho kinase-mediated sustained vasoconstriction, through increased Ca²⁺ sensitivity, plays an important role in the established PH and that RhoA/Rho kinase signaling contributes significantly to the development of PH and lung dysplasia in mild hypoxia-exposed FHR.

Ca²⁺ sensitivity; fasudil; vascular remodeling; lung dysplasia

This article has been cited by other articles:

				J. Gien, G. J. Seedorf, V. Balasubramaniam, N. Tseng, N. Markham, and S. H. Abman Chronic intrauterine pulmonary hypertension increases endothelial cell Rho kinase activity and impairs angiogenesis in vitro Am J Physiol Lung Cell Mol Physiol, October 1, 2008; 295(4): L680 - L687. [Abstract] [Full Text] [PDF]

				P. Tourneux, M. Chester, T. Grover, and S. H. Abman Fasudil inhibits the myogenic response in the fetal pulmonary circulation Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1505 - H1513. [Abstract] [Full Text] [PDF]

				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]

				A. R. Hemnes, A. Zaiman, and H. C. Champion 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, January 1, 2008; 294(1): L24 - L33. [Abstract] [Full Text] [PDF]

				G. Lagna, M. M. Ku, P. H. Nguyen, N. A. Neuman, B. N. Davis, and A. Hata Control of Phenotypic Plasticity of Smooth Muscle Cells by Bone Morphogenetic Protein Signaling through the Myocardin-related Transcription Factors J. Biol. Chem., December 21, 2007; 282(51): 37244 - 37255. [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]

				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]

				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]

				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]

				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]