| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles in PresS, published online ahead of print October 24, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00493.2002
Submitted on June 13, 2002
Accepted on October 17, 2002
1 Pediatrics, University of California, San Francisco, San Francisco, CA, USA
2 Cardiothoracic Surgery, University of California, San Francisco, San Francisco, CA, USA
3 Pediatrics, Northwestern University, Chicago, IL, USA
4 Pediatrics, University of California, San Francisco, San Francisco, CA, USA; Cardiovascular Research Institute, San Francisco, CA, USA
* To whom correspondence should be addressed. E-mail: jfineman{at}pedcard.ucsf.edu.
Altered pulmonary vascular reactivity is a source of morbidity and mortality for children with congenital heart disease and increased pulmonary blood flow. Nitric oxide (NO) and endothelin-1 (ET-1) are important mediators of pulmonary vascular reactivity. We hypothesize that early alterations in endothelial function contribute to the altered vascular reactivity associated with congenital heart disease. The objective of this study was to characterize endothelial function in our lamb model of increased pulmonary blood flow at one week of life. Eleven fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt), and were studied 7 days after delivery. The pulmonary vasodilator response to both intravenous acetylcholine (endothelium-dependent) and inhaled NO (endothelium-independent) was similar in shunt and control lambs. In addition, tissue NOx, NO synthase (NOS) activity, and eNOS protein levels were similar. Conversely, the vasodilator response to both ET-1 and 4Ala-ET-1 (an ETB receptor agonist) were attenuated in shunt lambs, and tissue ET-1 concentrations were increased (P<0.05). Associated with these changes were an increase in ECE-1 protein and a decrease in ETB receptor protein levels (P<0.05). These data demonstrate that increased pulmonary blood flow induces alterations in ET-1 signaling before NO signaling, and suggest an early role for ET-1 in the altered vascular reactivity associated with increased pulmonary blood flow.
This article has been cited by other articles:
|
|
 |
|
  P. E. Oishi, D. A. Wiseman, S. Sharma, S. Kumar, Y. Hou, S. A. Datar, A. Azakie, M. J. Johengen, C. Harmon, S. Fratz, et al. Progressive dysfunction of nitric oxide synthase in a lamb model of chronically increased pulmonary blood flow: a role for oxidative stress Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L756 - L766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sharma, A. C. Grobe, D. A. Wiseman, S. Kumar, M. Englaish, I. Najwer, E. Benavidez, P. Oishi, A. Azakie, J. R. Fineman, et al. Lung antioxidant enzymes are regulated by development and increased pulmonary blood flow Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L960 - L971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Lee, R. F. Gonzalez, C. J. Chapin, J. Busch, J. R. Fineman, and J. A. Gutierrez Nitric oxide decreases surfactant protein gene expression in primary cultures of type II pneumocytes Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L950 - L957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Lee, B. Ovadia, A. Azakie, S. Salas, J. Goerke, J. R. Fineman, and J. A. Gutierrez Increased pulmonary blood flow does not alter surfactant protein gene expression in lambs within the first week of life Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1237 - L1243. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
