Aerosol gene transfer with inducible nitric oxide synthase reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats

W. Budts, P. Pokreisz, Z. Nong, N. Van Pelt, H. Gillijns, R. Gerard, R. Lyons, D. Collen, K. D. Bloch, S. Janssens

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Background - Nitric oxide (NO) is a potent vasodilator with an important role in the regulation of pulmonary vascular tone. The effects of NO synthase (NOS) gene transfer on pulmonary vascular remodeling associated with hypoxic pulmonary hypertension are unknown. Methods and Results - We aerosolized 3 x 109 pfu of an adenoviral vector containing inducible NOS gene (AdNOS2), constitutive NOS3 gene (AdNOS3), or no transgene (AdRR5) into rat lungs. Exhaled NO levels, monitored with chemiluminescence, were higher in AdNOS2-infected rats than in AdNOS3- and AdRR5-infected rats (at 3 days, 33±6 ppb, n=9, versus 17±4, n=9, and 6±2 ppb, n=3, P<0.05 for both). Exposure to FIO2 0.10 for 7 days increased pulmonary artery pressure from 19±4 mm Hg (baseline) to 27± 1 and 26±2 mm Hg in AdNOS3- and AdRR5-infected rats, respectively, but only to 21±1 mm Hg in AdNOS2-infected animals (P<0.05). After 7 days of hypoxia, total pulmonary resistance in AdRR5- and AdNOS3-infected rats was significantly higher than in AdNOS2-infected animals (0.41±0.05 and 0.39±0.07 versus 0.35±0.03 mm Hg · mL-1 · min-1, respectively, P<0.05). Right ventricular hypertrophy was reduced in AdNOS2-infected rats [right ventricular/(left ventricular+septal) weight, 0.19±0.10 versus 0.28±0.10 and 0.32±0.10 in AdRR5- and AdNOS3-infected rats, respectively, P<0.05]. The percentage of muscularized precapillary pulmonary resistance vessels was also significantly decreased (18±4% versus 25±8% and 30±5% in AdRR5- and AdNOS3-infected rats, P<0.05). Conclusions - Aerosol NOS2 gene transfer increases pulmonary NO production and significantly reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling. Aerosol NOS2 gene transfer may be a promising strategy to target pulmonary vascular disorders.

Original languageEnglish (US)
Pages (from-to)2880-2885
Number of pages6
JournalCirculation
Volume102
Issue number23
StatePublished - Dec 5 2000

Fingerprint

Nitric Oxide Synthase Type II
Aerosols
Pulmonary Hypertension
Lung
Genes
Nitric Oxide
Nitric Oxide Synthase
Blood Vessels
Vascular Remodeling
Right Ventricular Hypertrophy
Luminescence
Vasodilator Agents
Transgenes
Pulmonary Artery
Pressure
Weights and Measures

Keywords

  • Genes
  • Hypertension, pulmonary
  • Nitric oxide synthase
  • Remodeling
  • Vasculature

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Budts, W., Pokreisz, P., Nong, Z., Van Pelt, N., Gillijns, H., Gerard, R., ... Janssens, S. (2000). Aerosol gene transfer with inducible nitric oxide synthase reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats. Circulation, 102(23), 2880-2885.

Aerosol gene transfer with inducible nitric oxide synthase reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats. / Budts, W.; Pokreisz, P.; Nong, Z.; Van Pelt, N.; Gillijns, H.; Gerard, R.; Lyons, R.; Collen, D.; Bloch, K. D.; Janssens, S.

In: Circulation, Vol. 102, No. 23, 05.12.2000, p. 2880-2885.

Research output: Contribution to journalArticle

Budts, W, Pokreisz, P, Nong, Z, Van Pelt, N, Gillijns, H, Gerard, R, Lyons, R, Collen, D, Bloch, KD & Janssens, S 2000, 'Aerosol gene transfer with inducible nitric oxide synthase reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats', Circulation, vol. 102, no. 23, pp. 2880-2885.
Budts W, Pokreisz P, Nong Z, Van Pelt N, Gillijns H, Gerard R et al. Aerosol gene transfer with inducible nitric oxide synthase reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats. Circulation. 2000 Dec 5;102(23):2880-2885.
Budts, W. ; Pokreisz, P. ; Nong, Z. ; Van Pelt, N. ; Gillijns, H. ; Gerard, R. ; Lyons, R. ; Collen, D. ; Bloch, K. D. ; Janssens, S. / Aerosol gene transfer with inducible nitric oxide synthase reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats. In: Circulation. 2000 ; Vol. 102, No. 23. pp. 2880-2885.
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abstract = "Background - Nitric oxide (NO) is a potent vasodilator with an important role in the regulation of pulmonary vascular tone. The effects of NO synthase (NOS) gene transfer on pulmonary vascular remodeling associated with hypoxic pulmonary hypertension are unknown. Methods and Results - We aerosolized 3 x 109 pfu of an adenoviral vector containing inducible NOS gene (AdNOS2), constitutive NOS3 gene (AdNOS3), or no transgene (AdRR5) into rat lungs. Exhaled NO levels, monitored with chemiluminescence, were higher in AdNOS2-infected rats than in AdNOS3- and AdRR5-infected rats (at 3 days, 33±6 ppb, n=9, versus 17±4, n=9, and 6±2 ppb, n=3, P<0.05 for both). Exposure to FIO2 0.10 for 7 days increased pulmonary artery pressure from 19±4 mm Hg (baseline) to 27± 1 and 26±2 mm Hg in AdNOS3- and AdRR5-infected rats, respectively, but only to 21±1 mm Hg in AdNOS2-infected animals (P<0.05). After 7 days of hypoxia, total pulmonary resistance in AdRR5- and AdNOS3-infected rats was significantly higher than in AdNOS2-infected animals (0.41±0.05 and 0.39±0.07 versus 0.35±0.03 mm Hg · mL-1 · min-1, respectively, P<0.05). Right ventricular hypertrophy was reduced in AdNOS2-infected rats [right ventricular/(left ventricular+septal) weight, 0.19±0.10 versus 0.28±0.10 and 0.32±0.10 in AdRR5- and AdNOS3-infected rats, respectively, P<0.05]. The percentage of muscularized precapillary pulmonary resistance vessels was also significantly decreased (18±4{\%} versus 25±8{\%} and 30±5{\%} in AdRR5- and AdNOS3-infected rats, P<0.05). Conclusions - Aerosol NOS2 gene transfer increases pulmonary NO production and significantly reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling. Aerosol NOS2 gene transfer may be a promising strategy to target pulmonary vascular disorders.",
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T1 - Aerosol gene transfer with inducible nitric oxide synthase reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats

AU - Budts, W.

AU - Pokreisz, P.

AU - Nong, Z.

AU - Van Pelt, N.

AU - Gillijns, H.

AU - Gerard, R.

AU - Lyons, R.

AU - Collen, D.

AU - Bloch, K. D.

AU - Janssens, S.

PY - 2000/12/5

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N2 - Background - Nitric oxide (NO) is a potent vasodilator with an important role in the regulation of pulmonary vascular tone. The effects of NO synthase (NOS) gene transfer on pulmonary vascular remodeling associated with hypoxic pulmonary hypertension are unknown. Methods and Results - We aerosolized 3 x 109 pfu of an adenoviral vector containing inducible NOS gene (AdNOS2), constitutive NOS3 gene (AdNOS3), or no transgene (AdRR5) into rat lungs. Exhaled NO levels, monitored with chemiluminescence, were higher in AdNOS2-infected rats than in AdNOS3- and AdRR5-infected rats (at 3 days, 33±6 ppb, n=9, versus 17±4, n=9, and 6±2 ppb, n=3, P<0.05 for both). Exposure to FIO2 0.10 for 7 days increased pulmonary artery pressure from 19±4 mm Hg (baseline) to 27± 1 and 26±2 mm Hg in AdNOS3- and AdRR5-infected rats, respectively, but only to 21±1 mm Hg in AdNOS2-infected animals (P<0.05). After 7 days of hypoxia, total pulmonary resistance in AdRR5- and AdNOS3-infected rats was significantly higher than in AdNOS2-infected animals (0.41±0.05 and 0.39±0.07 versus 0.35±0.03 mm Hg · mL-1 · min-1, respectively, P<0.05). Right ventricular hypertrophy was reduced in AdNOS2-infected rats [right ventricular/(left ventricular+septal) weight, 0.19±0.10 versus 0.28±0.10 and 0.32±0.10 in AdRR5- and AdNOS3-infected rats, respectively, P<0.05]. The percentage of muscularized precapillary pulmonary resistance vessels was also significantly decreased (18±4% versus 25±8% and 30±5% in AdRR5- and AdNOS3-infected rats, P<0.05). Conclusions - Aerosol NOS2 gene transfer increases pulmonary NO production and significantly reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling. Aerosol NOS2 gene transfer may be a promising strategy to target pulmonary vascular disorders.

AB - Background - Nitric oxide (NO) is a potent vasodilator with an important role in the regulation of pulmonary vascular tone. The effects of NO synthase (NOS) gene transfer on pulmonary vascular remodeling associated with hypoxic pulmonary hypertension are unknown. Methods and Results - We aerosolized 3 x 109 pfu of an adenoviral vector containing inducible NOS gene (AdNOS2), constitutive NOS3 gene (AdNOS3), or no transgene (AdRR5) into rat lungs. Exhaled NO levels, monitored with chemiluminescence, were higher in AdNOS2-infected rats than in AdNOS3- and AdRR5-infected rats (at 3 days, 33±6 ppb, n=9, versus 17±4, n=9, and 6±2 ppb, n=3, P<0.05 for both). Exposure to FIO2 0.10 for 7 days increased pulmonary artery pressure from 19±4 mm Hg (baseline) to 27± 1 and 26±2 mm Hg in AdNOS3- and AdRR5-infected rats, respectively, but only to 21±1 mm Hg in AdNOS2-infected animals (P<0.05). After 7 days of hypoxia, total pulmonary resistance in AdRR5- and AdNOS3-infected rats was significantly higher than in AdNOS2-infected animals (0.41±0.05 and 0.39±0.07 versus 0.35±0.03 mm Hg · mL-1 · min-1, respectively, P<0.05). Right ventricular hypertrophy was reduced in AdNOS2-infected rats [right ventricular/(left ventricular+septal) weight, 0.19±0.10 versus 0.28±0.10 and 0.32±0.10 in AdRR5- and AdNOS3-infected rats, respectively, P<0.05]. The percentage of muscularized precapillary pulmonary resistance vessels was also significantly decreased (18±4% versus 25±8% and 30±5% in AdRR5- and AdNOS3-infected rats, P<0.05). Conclusions - Aerosol NOS2 gene transfer increases pulmonary NO production and significantly reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling. Aerosol NOS2 gene transfer may be a promising strategy to target pulmonary vascular disorders.

KW - Genes

KW - Hypertension, pulmonary

KW - Nitric oxide synthase

KW - Remodeling

KW - Vasculature

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