Smooth muscle F-actin disassembly and RhoA/Rho-kinase signaling during endotoxin-induced alterations in pulmonary arterial compliance

Christa Boer, Geerten P. Van Nieuw Amerongen, A. B.Johan Groeneveld, Gert Jan Scheffer, Jaap J. De Lange, Nico Westerhof, Victor W.M. Van Hinsbergh, Pieter Sipkema

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Endotoxemia is associated with changed pulmonary vascular function with respect to vasoreactivity, endothelial permeability, and activation of inducible nitric oxide synthase II (NOSII). However, whether altered passive arterial wall mechanics contribute to this endotoxin-induced pulmonary vascular dysfunction is still unknown. Therefore, we investigated whether endotoxin affects the passive arterial mechanics and compliance of isolated rat pulmonary arteries. Pulmonary arteries of pentobarbital-anesthetized Wistar rats (n = 55) were isolated and exposed to Escherichia coli endotoxin (50 μg/ml) for 20 h. Endotoxin increased pulmonary artery diameter and compliance (transmural pressure = 13 mmHg) in an endothelium-, Ca2+, or NOSII-induced NO release-independent manner. Interestingly, the endotoxin- induced alterations in the passive arterial mechanics were accompanied by disassembly of the smooth muscle cell (SMC) F-actin cytoskeleton. Disassembly of F-actin by incubation of control arteries with the cytoskeleton-disrupting agent cytochalasin B or the Rho-kinase inhibitor Y-27632 induced a similar increase in passive arterial diameter and compliance. In contrast, RhoA activation by lysophosphatidic acid prevented the endotoxin-induced alterations in the pulmonary SMC F-actin cytoskeleton and passive mechanics. In conclusion, these findings indicate that disassembly of the SMC F-actin cytoskeleton and RhoA/Rho-kinase signaling act as mediators of endotoxin-induced changes in the pulmonary arterial mechanics. They imply the involvement of F-actin rearrangement and RhoA/Rho-kinase signaling in endotoxemia-induced vascular lung injury.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume287
Issue number4 31-4
DOIs
Publication statusPublished - 1 Oct 2004

Cite this

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title = "Smooth muscle F-actin disassembly and RhoA/Rho-kinase signaling during endotoxin-induced alterations in pulmonary arterial compliance",
abstract = "Endotoxemia is associated with changed pulmonary vascular function with respect to vasoreactivity, endothelial permeability, and activation of inducible nitric oxide synthase II (NOSII). However, whether altered passive arterial wall mechanics contribute to this endotoxin-induced pulmonary vascular dysfunction is still unknown. Therefore, we investigated whether endotoxin affects the passive arterial mechanics and compliance of isolated rat pulmonary arteries. Pulmonary arteries of pentobarbital-anesthetized Wistar rats (n = 55) were isolated and exposed to Escherichia coli endotoxin (50 μg/ml) for 20 h. Endotoxin increased pulmonary artery diameter and compliance (transmural pressure = 13 mmHg) in an endothelium-, Ca2+, or NOSII-induced NO release-independent manner. Interestingly, the endotoxin- induced alterations in the passive arterial mechanics were accompanied by disassembly of the smooth muscle cell (SMC) F-actin cytoskeleton. Disassembly of F-actin by incubation of control arteries with the cytoskeleton-disrupting agent cytochalasin B or the Rho-kinase inhibitor Y-27632 induced a similar increase in passive arterial diameter and compliance. In contrast, RhoA activation by lysophosphatidic acid prevented the endotoxin-induced alterations in the pulmonary SMC F-actin cytoskeleton and passive mechanics. In conclusion, these findings indicate that disassembly of the SMC F-actin cytoskeleton and RhoA/Rho-kinase signaling act as mediators of endotoxin-induced changes in the pulmonary arterial mechanics. They imply the involvement of F-actin rearrangement and RhoA/Rho-kinase signaling in endotoxemia-induced vascular lung injury.",
keywords = "Cytoskeleton, Lung injury, Lysophosphatidic acid, Passive mechanical arterial properties, Y-27632",
author = "Christa Boer and {Van Nieuw Amerongen}, {Geerten P.} and Groeneveld, {A. B.Johan} and Scheffer, {Gert Jan} and {De Lange}, {Jaap J.} and Nico Westerhof and {Van Hinsbergh}, {Victor W.M.} and Pieter Sipkema",
year = "2004",
month = "10",
day = "1",
doi = "10.1152/ajplung.00219.2003",
language = "English",
volume = "287",
journal = "American Journal of Physiology. Lung Cellular and Molecular Physiology",
issn = "1040-0605",
publisher = "American Physiological Society",
number = "4 31-4",

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Smooth muscle F-actin disassembly and RhoA/Rho-kinase signaling during endotoxin-induced alterations in pulmonary arterial compliance. / Boer, Christa; Van Nieuw Amerongen, Geerten P.; Groeneveld, A. B.Johan; Scheffer, Gert Jan; De Lange, Jaap J.; Westerhof, Nico; Van Hinsbergh, Victor W.M.; Sipkema, Pieter.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 287, No. 4 31-4, 01.10.2004.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Smooth muscle F-actin disassembly and RhoA/Rho-kinase signaling during endotoxin-induced alterations in pulmonary arterial compliance

AU - Boer, Christa

AU - Van Nieuw Amerongen, Geerten P.

AU - Groeneveld, A. B.Johan

AU - Scheffer, Gert Jan

AU - De Lange, Jaap J.

AU - Westerhof, Nico

AU - Van Hinsbergh, Victor W.M.

AU - Sipkema, Pieter

PY - 2004/10/1

Y1 - 2004/10/1

N2 - Endotoxemia is associated with changed pulmonary vascular function with respect to vasoreactivity, endothelial permeability, and activation of inducible nitric oxide synthase II (NOSII). However, whether altered passive arterial wall mechanics contribute to this endotoxin-induced pulmonary vascular dysfunction is still unknown. Therefore, we investigated whether endotoxin affects the passive arterial mechanics and compliance of isolated rat pulmonary arteries. Pulmonary arteries of pentobarbital-anesthetized Wistar rats (n = 55) were isolated and exposed to Escherichia coli endotoxin (50 μg/ml) for 20 h. Endotoxin increased pulmonary artery diameter and compliance (transmural pressure = 13 mmHg) in an endothelium-, Ca2+, or NOSII-induced NO release-independent manner. Interestingly, the endotoxin- induced alterations in the passive arterial mechanics were accompanied by disassembly of the smooth muscle cell (SMC) F-actin cytoskeleton. Disassembly of F-actin by incubation of control arteries with the cytoskeleton-disrupting agent cytochalasin B or the Rho-kinase inhibitor Y-27632 induced a similar increase in passive arterial diameter and compliance. In contrast, RhoA activation by lysophosphatidic acid prevented the endotoxin-induced alterations in the pulmonary SMC F-actin cytoskeleton and passive mechanics. In conclusion, these findings indicate that disassembly of the SMC F-actin cytoskeleton and RhoA/Rho-kinase signaling act as mediators of endotoxin-induced changes in the pulmonary arterial mechanics. They imply the involvement of F-actin rearrangement and RhoA/Rho-kinase signaling in endotoxemia-induced vascular lung injury.

AB - Endotoxemia is associated with changed pulmonary vascular function with respect to vasoreactivity, endothelial permeability, and activation of inducible nitric oxide synthase II (NOSII). However, whether altered passive arterial wall mechanics contribute to this endotoxin-induced pulmonary vascular dysfunction is still unknown. Therefore, we investigated whether endotoxin affects the passive arterial mechanics and compliance of isolated rat pulmonary arteries. Pulmonary arteries of pentobarbital-anesthetized Wistar rats (n = 55) were isolated and exposed to Escherichia coli endotoxin (50 μg/ml) for 20 h. Endotoxin increased pulmonary artery diameter and compliance (transmural pressure = 13 mmHg) in an endothelium-, Ca2+, or NOSII-induced NO release-independent manner. Interestingly, the endotoxin- induced alterations in the passive arterial mechanics were accompanied by disassembly of the smooth muscle cell (SMC) F-actin cytoskeleton. Disassembly of F-actin by incubation of control arteries with the cytoskeleton-disrupting agent cytochalasin B or the Rho-kinase inhibitor Y-27632 induced a similar increase in passive arterial diameter and compliance. In contrast, RhoA activation by lysophosphatidic acid prevented the endotoxin-induced alterations in the pulmonary SMC F-actin cytoskeleton and passive mechanics. In conclusion, these findings indicate that disassembly of the SMC F-actin cytoskeleton and RhoA/Rho-kinase signaling act as mediators of endotoxin-induced changes in the pulmonary arterial mechanics. They imply the involvement of F-actin rearrangement and RhoA/Rho-kinase signaling in endotoxemia-induced vascular lung injury.

KW - Cytoskeleton

KW - Lung injury

KW - Lysophosphatidic acid

KW - Passive mechanical arterial properties

KW - Y-27632

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U2 - 10.1152/ajplung.00219.2003

DO - 10.1152/ajplung.00219.2003

M3 - Article

VL - 287

JO - American Journal of Physiology. Lung Cellular and Molecular Physiology

JF - American Journal of Physiology. Lung Cellular and Molecular Physiology

SN - 1040-0605

IS - 4 31-4

ER -