Asthma is a chronic disease characterized by increased airway responsiveness and airway inflammation. The functional role of nitric oxide (NO) and the various nitric oxide synthase (NOS) isoforms in human asthma is controversial. To investigate the role of NO in an established model of allergic asthma, mice with targeted deletions of the three known isoforms of NOS (NOS1, 2, and 3) were studied. Although the inducible (NOS2) isoform was significantly upregulated in the lungs of ovalbumin (OVA)-sensitized and -challenged (OVA/OVA) wild-type (WT) mice and was undetectable in similarly treated NOS2-deficient mice, airway responsiveness was not significantly different between these groups. OVA/OVA endothelial (NOS3)-deficient mice were significantly more responsive to methacholine challenge compared with similarly treated NOS1 and NOS1&3-deficient mice. Airway responsiveness in OVA/OVA neuronal (NOS1)-deficient and neuronal/endothelial (NOS1&3) double-deficient mice was significantly less than that observed in similarly treated NOS2 and WT groups. These findings demonstrate an important function for the nNOS isoform in controlling the inducibility of airway hyperresponsiveness in this model of allergic asthma.
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17 May 1999
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May 17 1999
Contribution of Nitric Oxide Synthases 1, 2, and 3 to Airway Hyperresponsiveness and Inflammation in a Murine Model of Asthma
George T. De Sanctis,
George T. De Sanctis
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
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James A. MacLean,
James A. MacLean
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
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Kaoru Hamada,
Kaoru Hamada
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
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Sanjay Mehta,
Sanjay Mehta
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
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Jeremy A. Scott,
Jeremy A. Scott
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
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Aiping Jiao,
Aiping Jiao
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
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Chandri N. Yandava,
Chandri N. Yandava
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
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Lester Kobzik,
Lester Kobzik
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
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Walter W. Wolyniec,
Walter W. Wolyniec
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
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Attila J. Fabian,
Attila J. Fabian
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
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Changaram S. Venugopal,
Changaram S. Venugopal
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
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Hartmut Grasemann,
Hartmut Grasemann
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
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Paul L. Huang,
Paul L. Huang
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
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Jeffrey M. Drazen
Jeffrey M. Drazen
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
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George T. De Sanctis
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
James A. MacLean
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
Kaoru Hamada
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
Sanjay Mehta
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
Jeremy A. Scott
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
Aiping Jiao
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
Chandri N. Yandava
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
Lester Kobzik
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
Walter W. Wolyniec
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
Attila J. Fabian
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
Changaram S. Venugopal
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
Hartmut Grasemann
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
Paul L. Huang
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
Jeffrey M. Drazen
From the *Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the §Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‖Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the **Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
Address correspondence to George T. De Sanctis, Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115. Phone: 617-278-0729; Fax: 617-732-7421; E-mail: [email protected]
The analysis of lung resistance was performed using software provided by Andrew Jackson (Biomedical Engineering at Boston University, Boston, MA).
Received:
December 17 1998
Revision Received:
March 09 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (10): 1621–1630.
Article history
Received:
December 17 1998
Revision Received:
March 09 1999
Citation
George T. De Sanctis, James A. MacLean, Kaoru Hamada, Sanjay Mehta, Jeremy A. Scott, Aiping Jiao, Chandri N. Yandava, Lester Kobzik, Walter W. Wolyniec, Attila J. Fabian, Changaram S. Venugopal, Hartmut Grasemann, Paul L. Huang, Jeffrey M. Drazen; Contribution of Nitric Oxide Synthases 1, 2, and 3 to Airway Hyperresponsiveness and Inflammation in a Murine Model of Asthma . J Exp Med 17 May 1999; 189 (10): 1621–1630. doi: https://doi.org/10.1084/jem.189.10.1621
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