| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Cardiovascular Pulmonary Research Laboratory and 3 Department of Physiology, University of Colorado Health Sciences Center, Denver, Colorado 80262; and 2 Harvard Medical School, Boston, Massachusetts 02114
Nitric oxide plays an important role in modulating pulmonary vascular tone. All three isoforms of nitric oxide synthase (NOS), neuronal (nNOS, NOS I), inducible (iNOS, NOS II), and endothelial (eNOS, NOS III), are expressed in the lung. Recent reports have suggested an important role for eNOS in the modulation of pulmonary vascular tone chronically; however, the relative contribution of the three isoforms to acute modulation of pulmonary vascular tone is uncertain. We therefore tested the effect of targeted disruption of each isoform on pulmonary vascular reactivity in transgenic mice. Isolated perfused mouse lungs were used to evaluate the effect of selective loss of pulmonary nNOS, iNOS, and eNOS with respect to hypoxic pulmonary vasoconstriction (HPV) and endothelium-dependent and -independent vasodilation. eNOS null mice had augmented HPV (225 ± 65% control, P < 0.02, mean ± SE) and absent endothelium-dependent vasodilation, whereas endothelium-independent vasodilation was preserved. HPV was minimally elevated in iNOS null mice and normal in nNOS null mice. Both nNOS and iNOS null mice had normal endothelium-dependent vasodilation. In wild-type lungs, nonselective NOS inhibition doubled HPV, whereas selective iNOS inhibition had no detectable effect. In intact, lightly sedated mice, right ventricular systolic pressure was elevated in eNOS-deficient (42.3 ± 1.2 mmHg, P < 0.001) and, to a lesser extent, in iNOS-deficient (37.2 ± 0.8 mmHg, P < 0.001) mice, whereas it was normal in nNOS-deficient mice (30.9 ± 0.7 mmHg, P = not significant) compared with wild-type controls (31.3 ± 0.7 mmHg). We conclude that in the normal murine pulmonary circulation 1) nNOS does not modulate tone, 2) eNOS-derived nitric oxide is the principle mediator of endothelium-dependent vasodilation in the pulmonary circulation, and 3) both eNOS and iNOS play a role in modulating basal tone chronically.
nitric oxide; pulmonary hypertension; vasoconstriction
This article has been cited by other articles:
|
|
 |
|
  D. B. Frank, J. Lowery, L. Anderson, M. Brink, J. Reese, and M. de Caestecker Increased susceptibility to hypoxic pulmonary hypertension in Bmpr2 mutant mice is associated with endothelial dysfunction in the pulmonary vasculature Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L98 - L109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Xu, O. Platoshyn, A. Makino, W. H. Dillmann, K. Akassoglou, C. V. Remillard, and J. X.-J. Yuan Characterization of agonist-induced vasoconstriction in mouse pulmonary artery Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H220 - H228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Leblais, E. Delannoy, F. Fresquet, H. Begueret, N. Bellance, S. Banquet, C. Allieres, L. Leroux, C. Desgranges, A. Gadeau, et al. {beta}-adrenergic relaxation in pulmonary arteries: preservation of the endothelial nitric oxide-dependent {beta}2 component in pulmonary hypertension Cardiovasc Res, January 1, 2008; 77(1): 202 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Liu, Y. Hotta, A. R. Graveline, O. V. Evgenov, E. S. Buys, K. D. Bloch, F. Ichinose, and W. M. Zapol Congenital NOS2 deficiency prevents impairment of hypoxic pulmonary vasoconstriction in murine ventilator-induced lung injury Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1300 - L1305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Coggins and K. D. Bloch Nitric Oxide in the Pulmonary Vasculature Arterioscler. Thromb. Vasc. Biol., September 1, 2007; 27(9): 1877 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. T. Demchenko, K. E. Welty-Wolf, B. W. Allen, and C. A. Piantadosi Similar but not the same: normobaric and hyperbaric pulmonary oxygen toxicity, the role of nitric oxide Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L229 - L238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Littler, C. A. Wehling, M. J. Wick, K. A. Fagan, C. D. Cool, R. O. Messing, and E. C. Dempsey Divergent contractile and structural responses of the murine PKC-{epsilon} null pulmonary circulation to chronic hypoxia Am J Physiol Lung Cell Mol Physiol, December 1, 2005; 289(6): L1083 - L1093. [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]
|
|
|
|
|
|
F. Spohr, A. J. M. Cornelissen, C. Busch, M. M. Gebhard, J. Motsch, E. O. Martin, and J. Weimann Role of endogenous nitric oxide in endotoxin-induced alteration of hypoxic pulmonary vasoconstriction in mice Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H823 - H831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Prado, E. A. Leick-Maldonado, V. Arata, D. I. Kasahara, M. A. Martins, and I. F. L. C. Tiberio Neurokinins and inflammatory cell iNOS expression in guinea pigs with chronic allergic airway inflammation Am J Physiol Lung Cell Mol Physiol, April 1, 2005; 288(4): L741 - L748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Liu, O. V. Evgenov, and F. Ichinose NOS3 deficiency augments hypoxic pulmonary vasoconstriction and enhances systemic oxygenation during one-lung ventilation in mice J Appl Physiol, February 1, 2005; 98(2): 748 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Fagan, M. Oka, N. R. Bauer, S. A. Gebb, D. D. Ivy, K. G. Morris, and I. F. McMurtry Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of Rho-kinase Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L656 - L664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kavdia and A. S. Popel Contribution of nNOS- and eNOS-derived NO to microvascular smooth muscle NO exposure J Appl Physiol, July 1, 2004; 97(1): 293 - 301. [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]
|
|
|
|
|
|
M. P. Hlastala, W. J. E. Lamm, A. Karp, N. L. Polissar, I. R. Starr, and R. W. Glenny Spatial distribution of hypoxic pulmonary vasoconstriction in the supine pig J Appl Physiol, May 1, 2004; 96(5): 1589 - 1599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Enkhbaatar, K. Murakami, K. Shimoda, A. Mizutani, R. McGuire, F. Schmalstieg, R. Cox, H. Hawkins, J. Jodoin, S. Lee, et al. Inhibition of neuronal nitric oxide synthase by 7-nitroindazole attenuates acute lung injury in an ovine model Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2003; 285(2): R366 - R372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Vaughan, T. V. Brogan, M. E. Kerr, S. Deem, D. L. Luchtel, and E. R. Swenson Contributions of nitric oxide synthase isozymes to exhaled nitric oxide and hypoxic pulmonary vasoconstriction in rabbit lungs Am J Physiol Lung Cell Mol Physiol, May 1, 2003; 284(5): L834 - L843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Littler, K. G. Morris Jr., K. A. Fagan, I. F. McMurtry, R. O. Messing, and E. C. Dempsey Protein kinase C-epsilon -null mice have decreased hypoxic pulmonary vasoconstriction Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1321 - H1331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Ortiz and J. L. Garvin Cardiovascular and renal control in NOS-deficient mouse models Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2003; 284(3): R628 - R638. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yang, K. K. K. Sheares, N. Davie, P. D. Upton, G. W. Taylor, J. Horsley, J. Wharton, and N. W. Morrell Hypoxic Induction of Cox-2 Regulates Proliferation of Human Pulmonary Artery Smooth Muscle Cells Am. J. Respir. Cell Mol. Biol., December 1, 2002; 27(6): 688 - 696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fujita, R. J. Mason, C. Cool, J. M. Shannon, N. Hara, and K. A. Fagan Pulmonary hypertension in TNF-alpha -overexpressing mice is associated with decreased VEGF gene expression J Appl Physiol, December 1, 2002; 93(6): 2162 - 2170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. PAREDI, S. A. KHARITONOV, and P. J. BARNES Faster Rise of Exhaled Breath Temperature in Asthma . A Novel Marker of Airway Inflammation? Am. J. Respir. Crit. Care Med., January 15, 2002; 165(2): 181 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. Pitt and C. M. St. Croix Complex Regulation of iNOS in Lung Am. J. Respir. Cell Mol. Biol., January 1, 2002; 26(1): 6 - 9. [Full Text] [PDF]
|
|
|
|
|
|
H. NUNES, D. LEBREC, M. MAZMANIAN, F. CAPRON, J. HELLER, K. A. TAZI, E. ZERBIB, E. DULMET, R. MOREAU, A. T. DINH-XUAN, et al. Role of Nitric Oxide in Hepatopulmonary Syndrome in Cirrhotic Rats Am. J. Respir. Crit. Care Med., September 1, 2001; 164(5): 879 - 885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Marczin and D. Royston Editorial I: Nitric oxide as mediator, marker and modulator of microvascular damage in ARDS Br. J. Anaesth., August 1, 2001; 87(2): 179 - 183. [Full Text] [PDF]
|
|
|
|
|
|
D. Li, V. E. Laubach, and R. A. Johns Upregulation of lung soluble guanylate cyclase during chronic hypoxia is prevented by deletion of eNOS Am J Physiol Lung Cell Mol Physiol, August 1, 2001; 281(2): L369 - L376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Fagan Physiological and Genomic Consequences of Intermittent Hypoxia: Selected Contribution: Pulmonary hypertension in mice following intermittent hypoxia J Appl Physiol, June 1, 2001; 90(6): 2502 - 2507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G. Sobey Potassium Channel Function in Vascular Disease Arterioscler. Thromb. Vasc. Biol., January 1, 2001; 21(1): 28 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Hampl and J. Herget Role of Nitric Oxide in the Pathogenesis of Chronic Pulmonary Hypertension Physiol Rev, October 1, 2000; 80(4): 1337 - 1372. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
