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A novel inhaled organic nitrate that affects pulmonary vascular tone in a piglet model of hypoxia-induced pulmonary hypertension.

Publication ,  Journal Article
Brandler, MD; Powell, SC; Craig, DM; Quick, G; McMahon, TJ; Goldberg, RN; Stamler, JS
Published in: Pediatr Res
September 2005

Persistent pulmonary hypertension of the newborn is characterized by elevated pulmonary vascular resistance after birth leading to right-to-left shunting and systemic arterial hypoxemia. Inhaled nitric oxide (NO) is effective in reducing the need for extracorporeal membrane oxygenation, but it has potential toxicities, especially in an oxygen-rich environment. A number of other NO-based molecules have been given by inhalation, but their structure-function relationships have not been established. Recent studies have raised the idea that toxic and beneficial properties can be separated. We synthesized a novel organic nitrate [ethyl nitrate (ENO2)], tested it in vitro, and administered it to hypoxic piglets. ENO2 lowered pulmonary artery pressure and raised the Po2 in arterial blood but did not alter systemic vascular resistance or methemoglobin levels. In addition, we tested the effect of ENO2 in the presence of the thiol glutathione, both in vivo and in vitro, and found its action to be enhanced. Although ENO2 is less potent than inhaled NO on a dose-equivalency basis, pretreatment of hypoxic animals with glutathione, which may be depleted in injured lungs, led to a markedly enhanced effect (largely mitigating the difference in potency). These results suggest that ENO2 may hold promise as a safe alternative to NO, particularly in hypoxemic conditions characterized by thiol depletion.

Duke Scholars

Published In

Pediatr Res

DOI

ISSN

0031-3998

Publication Date

September 2005

Volume

58

Issue

3

Start / End Page

531 / 536

Location

United States

Related Subject Headings

  • Swine
  • Pediatrics
  • Nitrates
  • Muscle, Smooth, Vascular
  • Muscle Tonus
  • Methemoglobin
  • Lung
  • Hypoxia
  • Hypertension, Pulmonary
  • Dose-Response Relationship, Drug
 

Citation

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MLA
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Brandler, M. D., Powell, S. C., Craig, D. M., Quick, G., McMahon, T. J., Goldberg, R. N., & Stamler, J. S. (2005). A novel inhaled organic nitrate that affects pulmonary vascular tone in a piglet model of hypoxia-induced pulmonary hypertension. Pediatr Res, 58(3), 531–536. https://doi.org/10.1203/01.PDR.0000179399.64025.37
Brandler, Michael D., Steven C. Powell, Damian M. Craig, George Quick, Timothy J. McMahon, Ronald N. Goldberg, and Jonathan S. Stamler. “A novel inhaled organic nitrate that affects pulmonary vascular tone in a piglet model of hypoxia-induced pulmonary hypertension.Pediatr Res 58, no. 3 (September 2005): 531–36. https://doi.org/10.1203/01.PDR.0000179399.64025.37.
Brandler MD, Powell SC, Craig DM, Quick G, McMahon TJ, Goldberg RN, et al. A novel inhaled organic nitrate that affects pulmonary vascular tone in a piglet model of hypoxia-induced pulmonary hypertension. Pediatr Res. 2005 Sep;58(3):531–6.
Brandler, Michael D., et al. “A novel inhaled organic nitrate that affects pulmonary vascular tone in a piglet model of hypoxia-induced pulmonary hypertension.Pediatr Res, vol. 58, no. 3, Sept. 2005, pp. 531–36. Pubmed, doi:10.1203/01.PDR.0000179399.64025.37.
Brandler MD, Powell SC, Craig DM, Quick G, McMahon TJ, Goldberg RN, Stamler JS. A novel inhaled organic nitrate that affects pulmonary vascular tone in a piglet model of hypoxia-induced pulmonary hypertension. Pediatr Res. 2005 Sep;58(3):531–536.

Published In

Pediatr Res

DOI

ISSN

0031-3998

Publication Date

September 2005

Volume

58

Issue

3

Start / End Page

531 / 536

Location

United States

Related Subject Headings

  • Swine
  • Pediatrics
  • Nitrates
  • Muscle, Smooth, Vascular
  • Muscle Tonus
  • Methemoglobin
  • Lung
  • Hypoxia
  • Hypertension, Pulmonary
  • Dose-Response Relationship, Drug