|
|
||||||||
Department of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205
Hypoxia (0%
O2) evokes a late-phase,
endothelium-dependent contractile response in porcine isolated
pulmonary arteries that may be caused by a cyclooxygenase-independent,
endothelium-derived contractile factor. The aim of this study was to
further analyze the mechanism underlying this hypoxic response.
Proximal porcine pulmonary arterial rings were suspended for isometric
tension recording in organ chambers. Hypoxia (0%
O2) caused a late-phase, endothelium-dependent contractile response that was not inhibited by
the endothelin (ET)A-receptor
antagonist BQ-123 (10
6 M),
by the ETB-receptor antagonist
BQ-788 (10
7 M), or by their
combination. In contrast, ET-1 caused a concentration-dependent contraction of arterial rings that was inhibited by BQ-123
(10
6 M) and a relaxation
that was abolished by BQ-788
(10
7 M) or by endothelial
cell removal. Therefore, the endothelium-dependent contraction to
hypoxia is not mediated by ET. Hypoxia caused only relaxation in
endothelium-denuded rings. However, when a pulmonary valve leaflet, a
rich source of pulmonary endothelial cells, was placed into the lumen
of endothelium-denuded rings, hypoxia caused a late-phase contractile
response that was similar to that observed in arterial rings with
native endothelium. This hypoxic contraction persisted in the presence
of indomethacin (10
5 M) and
N-nitro-L-arginine
methyl ester (3 × 10
5
M) to block cyclooxygenase and nitric oxide synthase, respectively. These results suggest that hypoxic contraction of pulmonary arteries is
mediated by a diffusible, contractile factor released from hypoxic
endothelial cells. This contractile mediator is distinct from ET.
endothelium; hypoxia; endothelinA receptor; endothelinB receptor; pulmonary valve leaflet; pulmonary artery; endothelium-derived contractile factor
This article has been cited by other articles:
![]() |
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] |
||||
![]() |
T. P. Robertson, P. I. Aaronson, and J. P. T. Ward Ca2+ sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent Am J Physiol Lung Cell Mol Physiol, June 1, 2003; 284(6): L1121 - L1126. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Kajino, Y.-Q. Chen, S. R. Seidner, N. Waleh, F. Mauray, C. Roman, S. Chemtob, C. J. Koch, and R. I. Clyman Factors that increase the contractile tone of the ductus arteriosus also regulate its anatomic remodeling Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2001; 281(1): R291 - R301. [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] |
||||
![]() |
H. Kajino, Y.-Q. Chen, S. Chemtob, N. Waleh, C. J. Koch, and R. I. Clyman Tissue hypoxia inhibits prostaglandin and nitric oxide production and prevents ductus arteriosus reopening Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2000; 279(1): R278 - R286. [Abstract] [Full Text] [PDF] |
||||
![]() |
K.-D. Schluter, C. Katzer, K. Frischkopf, S. Wenzel, G. Taimor, and H. M. Piper Expression, Release, and Biological Activity of Parathyroid Hormone-Related Peptide From Coronary Endothelial Cells Circ. Res., May 12, 2000; 86(9): 946 - 951. [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] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |