Published ahead of print on August 28, 2003, doi:10.1164/rccm.200304-562OC
Am. J. Respir. Crit. Care Med., Volume 168, Number 11, December 2003, 1391-1398
A more recent version of this article appeared on December 1, 2003
Submitted on April 23, 2003
Accepted on August 21, 2003
Stretch activates nitric oxide production in pulmonary vascular endothelial cells in situ
Wolfgang M Kuebler1, Ulrike Uhlig2, Torsten Goldmann2, Gregor Schael1, Alexander Kerem3, Kay Exner2, Christian Martin2, Ekkehard Vollmer2, and Stefan Uhlig2*
1 Institute of Physiology, Free University of Berlin, Berlin, Germany,
2 Division of Pulmonary Pharmacology, Free University of Berlin, Berlin, Germany,
3 Institute of Anesthesiology, Research Center Borstel, Deutsches Herzzentrum Berlin, Berlin, Germany; Institute of Physiology, Free University of Berlin, Berlin, Germany
* To whom correspondence should be addressed. E-mail: suhlig{at}fz-borstel.de.
Whereas endothelial responses to shear stress have been studied extensively, those to circumferential vascular stretch are yet poorly defined. Circumferential stretch in pulmonary microvessels is largely determined by the transmural pressure gradient, hence by both vascular perfusion and alveolar ventilation pressures. Here, we have studied the production of nitric oxide by the endothelial nitric oxide synthase in two different models of vascular stretch in the intact lung: In isolated-perfused rat lungs, vascular stretch was induced by elevation of vascular pressure. In situ digital fluorescence microscopy revealed stretch-dependent NO production, which was localized to capillary endothelial cells and inhibited by NO synthase blockers. In isolated-perfused mouse lungs, vascular stretch was generated by ventilation with elevated negative pressure. Stretch-induced phosphorylation of Akt and endothelial NO synthase in lung endothelial cells was demonstrated by immunohistochemistry, and increased NO production by in situ fluorescence microscopy. Stretch-induced endothelial responses in both models were abrogated by pretreatment with phosphatidylinositol-3-OH kinase inhibitors. These findings demonstrate that circumferential stretch activates NO production in pulmonary endothelial cells by a signaling cascade involving phosphatidylinositol-3-OH kinase, Akt and endothelial NO synthase, and that this response is independent from the mechanical factors causing vascular distension.
Key words: overventilation, hydrostatic stress, fluorescence microscopy, endothelial nitric oxide synthase, phosphatidylinositol-3-OH kinase
This article has been cited by other articles:
|
|
|
|
 
E. P. Schmidt, M. Damarla, O. Rentsendorj, L. E. Servinsky, B. Zhu, A. Moldobaeva, A. Gonzalez, P. M. Hassoun, and D. B. Pearse
Soluble guanylyl cyclase contributes to ventilator-induced lung injury in mice
Am J Physiol Lung Cell Mol Physiol,
December 1, 2008;
295(6):
L1056 - L1065.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Chen, C. A. Bosworth, T. Pico, J. F. Collawn, K. Varga, Z. Gao, J. P. Clancy, J. A. Fortenberry, J. R. Lancaster Jr., and S. Matalon
DETANO and Nitrated Lipids Increase Chloride Secretion across Lung Airway Cells
Am. J. Respir. Cell Mol. Biol.,
August 1, 2008;
39(2):
150 - 162.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Kiefmann, J. M. Rifkind, E. Nagababu, and J. Bhattacharya
Red blood cells induce hypoxic lung inflammation
Blood,
May 15, 2008;
111(10):
5205 - 5214.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Yin, J. Hoffmann, S. M. Kaestle, N. Neye, L. Wang, J. Baeurle, W. Liedtke, S. Wu, H. Kuppe, A. R. Pries, et al.
Negative-Feedback Loop Attenuates Hydrostatic Lung Edema via a cGMP-Dependent Regulation of Transient Receptor Potential Vanilloid 4
Circ. Res.,
April 25, 2008;
102(8):
966 - 974.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Liu, Y. Hotta, A. R. Graveline, O. V. Evgenov, E. S. Buys, K. D. Bloch, F. Ichinose, and W. M. Zapol
Congenital NOS2 deficiency prevents impairment of hypoxic pulmonary vasoconstriction in murine ventilator-induced lung injury
Am J Physiol Lung Cell Mol Physiol,
November 1, 2007;
293(5):
L1300 - L1305.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Kaestle, C. A. Reich, N. Yin, H. Habazettl, J. Weimann, and W. M. Kuebler
Nitric oxide-dependent inhibition of alveolar fluid clearance in hydrostatic lung edema
Am J Physiol Lung Cell Mol Physiol,
October 1, 2007;
293(4):
L859 - L869.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. O. Dull, I. Mecham, and S. McJames
Heparan sulfates mediate pressure-induced increase in lung endothelial hydraulic conductivity via nitric oxide/reactive oxygen species
Am J Physiol Lung Cell Mol Physiol,
June 1, 2007;
292(6):
L1452 - L1458.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. N. Dedkova, Y. G. Wang, X. Ji, L. A. Blatter, A. M. Samarel, and S. L. Lipsius
Signalling mechanisms in contraction-mediated stimulation of intracellular NO production in cat ventricular myocytes
J. Physiol.,
April 1, 2007;
580(1):
327 - 345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. M. Kuebler, K. Parthasarathi, J. Lindert, and J. Bhattacharya
Real-time lung microscopy
J Appl Physiol,
March 1, 2007;
102(3):
1255 - 1264.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. A. Mohammed, N. Nasreen, R. S. Tepper, and V. B. Antony
Cyclic stretch induces PlGF expression in bronchial airway epithelial cells via nitric oxide release
Am J Physiol Lung Cell Mol Physiol,
February 1, 2007;
292(2):
L559 - L566.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G. Abraldes, Y. Iwakiri, M. Loureiro-Silva, O. Haq, W. C. Sessa, and R. J. Groszmann
Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state
Am J Physiol Gastrointest Liver Physiol,
May 1, 2006;
290(5):
G980 - G987.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Brueckl, S. Kaestle, A. Kerem, H. Habazettl, F. Krombach, H. Kuppe, and W. M. Kuebler
Hyperoxia-Induced Reactive Oxygen Species Formation in Pulmonary Capillary Endothelial Cells In Situ
Am. J. Respir. Cell Mol. Biol.,
April 1, 2006;
34(4):
453 - 463.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. T. Yiming, K. Parthasarathi, A. C. Issekutz, and S. Bhattacharya
Sequence of Endothelial Signaling during Lung Expansion
Am. J. Respir. Cell Mol. Biol.,
December 1, 2005;
33(6):
549 - 554.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Peng, R.-E. E. Abdulnour, S. Sammani, S.-F. Ma, E. J. Han, E. J. Hasan, R. Tuder, J. G. N. Garcia, and P. M. Hassoun
Inducible Nitric Oxide Synthase Contributes to Ventilator-induced Lung Injury
Am. J. Respir. Crit. Care Med.,
August 15, 2005;
172(4):
470 - 479.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hammerschmidt, H. Kuhn, U. Sack, A. Schlenska, C. Gessner, A. Gillissen, and H. Wirtz
Mechanical Stretch Alters Alveolar Type II Cell Mediator Release toward a Proinflammatory Pattern
Am. J. Respir. Cell Mol. Biol.,
August 1, 2005;
33(2):
203 - 210.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Caironi, F. Ichinose, R. Liu, R. C. Jones, K. D. Bloch, and W. M. Zapol
5-Lipoxygenase Deficiency Prevents Respiratory Failure during Ventilator-induced Lung Injury
Am. J. Respir. Crit. Care Med.,
August 1, 2005;
172(3):
334 - 343.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Ortiz, N. J. Hong, and J. L. Garvin
Luminal flow induces eNOS activation and translocation in the rat thick ascending limb
Am J Physiol Renal Physiol,
August 1, 2004;
287(2):
F274 - F280.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Tobin
Chronic Obstructive Pulmonary Disease, Pollution, Pulmonary Vascular Disease, Transplantation, Pleural Disease, and Lung Cancer in AJRCCM 2003
Am. J. Respir. Crit. Care Med.,
January 15, 2004;
169(2):
301 - 313.
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Uhlig, H. Fehrenbach, R. A. Lachmann, T. Goldmann, B. Lachmann, E. Vollmer, and S. Uhlig
Phosphoinositide 3-OH Kinase Inhibition Prevents Ventilation-induced Lung Cell Activation
Am. J. Respir. Crit. Care Med.,
January 15, 2004;
169(2):
201 - 208.
[Abstract]
[Full Text]
[PDF]
|
|
|
Copyright © 2003 American Thoracic Society
|
|
|
