| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Departments of Medicine and Physiology, Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226; and 2 Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709
Arachidonic acid metabolites of the cyclooxygenase and lipoxygenase pathways have a variety of important lung functions. Recent observations indicate that cytochrome P-450 (P-450) monooxygenases are also expressed in the lung, localized to specific pulmonary cell types (e.g., epithelium, endothelium, and smooth muscle), and may modulate critical lung functions. This review summarizes recent data on the presence and biological activity of P-450-derived eicosanoids in the pulmonary vasculature and airways, including effects on pulmonary vascular and bronchial smooth muscle tone and airway epithelial ion transport. We hypothesize a number of potential functions of P-450-derived arachidonate metabolites in the lungs such as contribution to hypoxic pulmonary vasoconstriction, regulation of bronchomotor tone, control of the composition of airway lining fluid, and limitation of pulmonary inflammation. Finally, we describe a number of emerging technologies, including congenic and transgenic strains of experimental animals, P-450 isoform-specific inhibitors and inhibitory antibodies, eicosanoid analogs, and vectors for delivery of P-450 cDNAs and antisense oligonucleotides. These tools will facilitate further studies on the contribution of endogenously formed P-450 eicosanoid metabolites to lung function, under both normal and pathological conditions.
arachidnoic acid; monooxygenases; eicosanoids; pulmonary arteries; bronchi; bronchospasm; cytochrome P-450; inflammation; hypoxic vasoconstriction; mitogenesis
This article has been cited by other articles:
|
|
 |
|
  C. Morin, M. Sirois, V. Echave, E. Rizcallah, and E. Rousseau Relaxing effects of 17(18)-EpETE on arterial and airway smooth muscles in human lung Am J Physiol Lung Cell Mol Physiol, January 1, 2009; 296(1): L130 - L139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Medhora, Y. Chen, S. Gruenloh, D. Harland, S. Bodiga, J. Zielonka, D. Gebremedhin, Y. Gao, J. R. Falck, S. Anjaiah, et al. 20-HETE increases superoxide production and activates NAPDH oxidase in pulmonary artery endothelial cells Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L902 - L911. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Morin, C. Guibert, M. Sirois, V. Echave, M. M. Gomes, and E. Rousseau Effects of {omega}-hydroxylase product on distal human pulmonary arteries Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1435 - H1443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Morin, M. Sirois, V. Echave, M. M. Gomes, and E. Rousseau Functional effects of 20-HETE on human bronchi: hyperpolarization and relaxation due to BKCa channel activation Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L1037 - L1044. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Morin, M. Sirois, V. Echave, M. M. Gomes, and E. Rousseau Epoxyeicosatrienoic Acid Relaxing Effects Involve Ca2+-Activated K+ Channel Activation and CPI-17 Dephosphorylation in Human Bronchi Am. J. Respir. Cell Mol. Biol., May 1, 2007; 36(5): 633 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Nieves and J. J. Moreno Hydroxyeicosatetraenoic acids released through the cytochrome P-450 pathway regulate 3T6 fibroblast growth J. Lipid Res., December 1, 2006; 47(12): 2681 - 2689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Weissmann, N. Sommer, R. T. Schermuly, H. A. Ghofrani, W. Seeger, and F. Grimminger Oxygen sensors in hypoxic pulmonary vasoconstriction Cardiovasc Res, September 1, 2006; 71(4): 620 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Dhanasekaran, R. Al-Saghir, B. Lopez, D. Zhu, D. D. Gutterman, E. R. Jacobs, and M. Medhora Protective effects of epoxyeicosatrienoic acids on human endothelial cells from the pulmonary and coronary vasculature Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H517 - H531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Parker, T. R. Grover, J. P. Kinsella, J. R. Falck, and S. H. Abman Inhibition of 20-HETE abolishes the myogenic response during NOS antagonism in the ovine fetal pulmonary circulation Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L261 - L267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Jung, R. P. Brandes, I.-H. Kim, F. Schweda, R. Schmidt, B. D. Hammock, R. Busse, and I. Fleming Soluble Epoxide Hydrolase Is a Main Effector of Angiotensin II-Induced Hypertension Hypertension, April 1, 2005; 45(4): 759 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yaghi, J. R. Bend, C. D. Webb, D. C. Zeldin, S. Weicker, S. Mehta, and D. G. McCormack Excess nitric oxide decreases cytochrome P-450 2J4 content and P-450-dependent arachidonic acid metabolism in lungs of rats with acute pneumonia Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1260 - L1267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yaghi, J. A. Bradbury, D. C. Zeldin, S. Mehta, J. R. Bend, and D. G. McCormack Pulmonary cytochrome P-450 2J4 is reduced in a rat model of acute Pseudomonas pneumonia Am J Physiol Lung Cell Mol Physiol, November 1, 2003; 285(5): L1099 - L1105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Stephenson, R. S. Sprague, J. L. Losapio, and A. J. Lonigro Differential effects of 5,6-EET on segmental pulmonary vasoactivity in the rabbit Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2153 - H2161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Medhora, J. Daniels, K. Mundey, B. Fisslthaler, R. Busse, E. R. Jacobs, and D. R. Harder Epoxygenase-driven angiogenesis in human lung microvascular endothelial cells Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H215 - H224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yu, R. P. McAndrew, R. Al-Saghir, K. G. Maier, M. Medhora, R. J. Roman, and E. R. Jacobs Nitric oxide contributes to 20-HETE-induced relaxation of pulmonary arteries J Appl Physiol, October 1, 2002; 93(4): 1391 - 1399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zhu, C. Zhang, M. Medhora, and E. R. Jacobs CYP4A mRNA, protein, and product in rat lungs: novel localization in vascular endothelium J Appl Physiol, July 1, 2002; 93(1): 330 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Roman P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function Physiol Rev, January 1, 2002; 82(1): 131 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Fleming Cytochrome P450 and Vascular Homeostasis Circ. Res., October 26, 2001; 89(9): 753 - 762. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
