|
|
||||||||
1 Integrative Biology Programme and 2 Division of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8; 3 Department of Physiology, School of Medicine, Chiba University, Chiba, 260-8670 Japan; and 4 Howard Hughes Medical Institute and Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75235
In vitro and in
vivo techniques were developed with genetically modified mice to
determine whether endothelin-1 (ET-1) functions as an
O2 mediator in closure of the
ductus arteriosus (DA) at birth. Wild-type CD-1 and 129/SvEv mice with
ETA receptor
/
, +/
, and +/+ genotypes were used. Isolated DA from term
ETA +/+ fetuses contracted to
O2 (5-95%) and a thromboxane
A2 analog (ONO-11113, 0.1 µM).
Instead, ET-1 elicited a dual response with weak relaxation (0.1 nM)
preceding contraction (1-100 nM). Indomethacin (2.8 µM) was also a constrictor. ETA
/
DA, unlike ETA +/+
DA, contracted marginally to O2
and ET-1 but responded to ONO-11113.
O2 contraction was also reduced in
ETA +/
DA. In vivo, DA
constricted equally in tracheotomized
ETA
/
and
ETA +/+ newborns. Conversely, no DA constriction was seen in hyperoxic
ETA
/
fetuses in
utero, although it occurred in ETA
+/+ and +/
littermates. We conclude that ET-1 mediates the DA
constrictor response to O2.
Without ET-1, however, the vessel still closes postnatally, conceivably caused by the withdrawal of relaxing influence(s).
oxygen; endothelin
This article has been cited by other articles:
![]() |
M. Costa, S. Barogi, N. D. Socci, D. Angeloni, M. Maffei, B. Baragatti, C. Chiellini, E. Grasso, and F. Coceani Gene expression in ductus arteriosus and aorta: comparison of birth and oxygen effects Physiol Genomics, April 13, 2006; 25(2): 250 - 262. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Coe, S. J. Haleen, K. M. Welch, Y.-A. Liu, and F. Coceani The Endothelin A Receptor Antagonists PD 156707 (CI-1020) and PD 180988 (CI-1034) Reverse the Hypoxic Pulmonary Vasoconstriction in the Perinatal Lamb J. Pharmacol. Exp. Ther., August 1, 2002; 302(2): 672 - 680. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |