| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Divisions of 1 Pediatric Critical Care and 2 Newborn Medicine, Department of Pediatrics, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada H3H 1P3
Nitric oxide (NO) is thought to play an important role in the regulation of neonatal pulmonary vasculature. It has been suggested that neonates with pulmonary hypertension have a defective NO pathway. Therefore, we measured in 1-day-old piglets exposed to hypoxia (fraction of inspired O2 = 0.10) for 3 or 14 days to induce pulmonary hypertension 1) the activity of NO synthase (NOS) via conversion of L-arginine to L-citrulline and the concentration of the NO precursor L-arginine in isolated pulmonary vessels, 2) the vasodilator response to the NO donor 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1) and the cGMP analog 8-bromo-cGMP in isolated perfused lungs, and 3) the production of cGMP in response to SIN-1 in isolated perfused lungs. After 3 days of exposure to hypoxia, endothelial NOS (eNOS) activity was unaffected, whereas, after 14 days of hypoxia, eNOS activity was decreased in the cytosolic fraction of pulmonary artery (P < 0.05) but not of pulmonary vein homogenates. Inducible NOS activity was decreased in the cytosolic fraction of pulmonary artery homogenates after both 3 (P < 0.05) and 14 (P < 0.05) days of hypoxia but was unchanged in pulmonary veins. Pulmonary artery levels of L-arginine were unaffected by hypoxic exposure. After 3 days of exposure to hypoxia, the reduction in the dilator response to SIN-1 (P < 0.05) coincided with a decrease in cGMP production (P < 0.005), suggesting that soluble guanylate cyclase activity may be altered. When the exposure was prolonged to 14 days, dilation to SIN-1 remained decreased (P < 0.05) and, although cGMP production normalized, the dilator response to 8-bromo-cGMP decreased (P < 0.05), suggesting that, after prolonged exposure to hypoxia, cGMP-dependent mechanisms may also be impaired. In conclusion, neonatal hypoxia-induced pulmonary hypertension is associated with multiple disruptions in the NO pathway.
endothelial nitric oxide synthase; inducible nitric oxide synthase; L-arginine; 3-morpholinosydnonimine-N-ethylcarbamide; guanosine 3',5'-cyclic monophosphate; isolated perfused lungs; pulmonary arteries; pulmonary veins
This article has been cited by other articles:
|
|
 |
|
  D. K. Hirenallur-S., S. T. Haworth, J. T. Leming, J. Chang, G. Hernandez, J. B. Gordon, and N. J. Rusch Upregulation of vascular calcium channels in neonatal piglets with hypoxia-induced pulmonary hypertension Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L915 - L924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Schindler, A. A. Hislop, and S. G. Haworth Postnatal changes in pulmonary vein responses to endothelin-1 in the normal and chronically hypoxic lung Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1273 - L1279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Gao, A. D. Portugal, S. Negash, W. Zhou, L. D. Longo, and J. Usha Raj Role of Rho kinases in PKG-mediated relaxation of pulmonary arteries of fetal lambs exposed to chronic high altitude hypoxia Am J Physiol Lung Cell Mol Physiol, March 1, 2007; 292(3): L678 - L684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Fike, Y. Zhang, and M. R. Kaplowitz Thromboxane inhibition reduces an early stage of chronic hypoxia-induced pulmonary hypertension in piglets J Appl Physiol, August 1, 2005; 99(2): 670 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Miller, A. A. Hislop, P. J. Vallance, and S. G. Haworth Deletion of the eNOS gene has a greater impact on the pulmonary circulation of male than female mice Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L299 - L366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-C. Chan, F.-P. Leung, X. Yao, C.-W. Lau, P. M. Vanhoutte, and Y. Huang Raloxifene Relaxes Rat Pulmonary Arteries and Veins: Roles of Gender, Endothelium, and Antagonism of Ca2+ Influx J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 1266 - 1271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Schindler, A. A. Hislop, and S. G. Haworth Postnatal Changes in Response to Norepinephrine in the Normal and Pulmonary Hypertensive Lung Am. J. Respir. Crit. Care Med., September 15, 2004; 170(6): 641 - 646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Fike, J. L. Aschner, Y. Zhang, and M. R. Kaplowitz Impaired NO signaling in small pulmonary arteries of chronically hypoxic newborn piglets Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1244 - L1254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Belik, R. P. Jankov, J. Pan, and A. K. Tanswell Chronic O2 exposure enhances vascular and airway smooth muscle contraction in the newborn but not adult rat J Appl Physiol, June 1, 2003; 94(6): 2303 - 2312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Turley, L. D. Nelin, M. R. Kaplowitz, Y. Zhang, and C. D. Fike Exhaled NO is reduced at an early stage of hypoxia-induced pulmonary hypertension in newborn piglets Am J Physiol Lung Cell Mol Physiol, March 1, 2003; 284(3): L489 - L500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Raj and L. Shimoda Oxygen-dependent signaling in pulmonary vascular smooth muscle Am J Physiol Lung Cell Mol Physiol, October 1, 2002; 283(4): L671 - L677. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Masuda, T. Tsujii, T. Okuno, K. Kihara, M. Goto, and H. Azuma Accumulated endogenous NOS inhibitors, decreased NOS activity, and impaired cavernosal relaxation with ischemia Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2002; 282(6): R1730 - R1738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Fike, S. L. Pfister, M. R. Kaplowitz, and J. A. Madden Cyclooxygenase contracting factors and altered pulmonary vascular responses in chronically hypoxic newborn pigs J Appl Physiol, January 1, 2002; 92(1): 67 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Karamsetty, J. R. Klinger, and N. S. Hill Phytoestrogens Restore Nitric Oxide-Mediated Relaxation in Isolated Pulmonary Arteries from Chronically Hypoxic Rats J. Pharmacol. Exp. Ther., June 1, 2001; 297(3): 968 - 974. [Abstract] [Full Text]
|
|
|
|
|
|
N. L. Jernigan and T. C. Resta Chronic hypoxia attenuates cGMP-dependent pulmonary vasodilation Am J Physiol Lung Cell Mol Physiol, June 1, 2002; 282(6): L1366 - L1375. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
