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Cited by 33Pulmonary Hypertension Research and TreatmentsVascular Anomalies and TreatmentsInhalation and Respiratory Drug Delivery

Prolonged inhaled NO attenuates hypoxic, but not monocrotaline-induced, pulmonary vascular remodeling in rats

Horstman, Damian J., Frank, Deborah U., Rich, George F.·1998·Anesthesia & Analgesia
DOI 10.1213/00000539-199801000-00015
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Abstract

In concentrations of 10-20 ppm, inhaled nitric oxide (NO) decreases pulmonary artery pressure and attenuates vascular remodeling in pulmonary hypertensive rats. Because NO is potentially toxic, it is important to know whether lower concentrations attenuate vascular remodeling produced by different etiologies. Therefore, we determined the effects of prolonged, small-dose inhaled NO administration on hypoxic and monocrotaline (MCT)-induced pulmonary vascular remodeling. Rats were subjected to normoxia, hypoxia (normobaric 10% oxygen), or hypoxia plus NO in concentrations of 50 ppb, 200 ppb, 2 ppm, 20 ppm, and 100 ppm for 3 wk. A second group of normoxic rats was given MCT (60 mg/kg intraperitoneally) alone or in the presence of 2, 20, and 100 ppm of NO. Subsequently, pulmonary artery smooth muscle thickness and the number of muscular arteries (percentage of total arteries) were determined. Right ventricular hypertrophy was determined by right to left ventricle plus septum weight ratio (RV/LV + S). Pulmonary artery smooth muscle thickness and the percent muscular arteries were increased by hypoxia and MCT. The hypoxic increase in thickness was attenuated by all concentrations of NO, with 100 ppm being greatest, whereas NO had no effect on MCT rats. NO attenuated the increase in percent muscular arteries in hypoxic but not MCT rats. The RV/LV + S was increased by hypoxia and MCT compared with normoxia. Hypoxia-induced RV hypertrophy was decreased by all concentrations of inhaled NO, although attenuation with 50 ppb was less than with 200 ppb, 20 ppm, and 100 ppm. In MCT rats 2 and 100 ppm NO increased RV hypertrophy, whereas 20 ppm had no effect. In conclusion, inhaled NO in concentrations as low as 50 ppb attenuates the pulmonary vascular remodeling and RV hypertrophy secondary to hypoxia. In contrast, concentrations as high as 100 ppm do not attenuate MCT-induced pulmonary remodeling. These results demonstrate that extremely low concentrations of NO may attenuate remodeling but that the effectiveness is dependent on the mechanism inducing pulmonary remodeling. Implications: The authors determined whether inhaled NO, a selective pulmonary vasodilator, attenuates pulmonary vascular remodeling caused by two models of pulmonary hypertension: chronic hypoxia and monocrotaline injection. Analysis of pulmonary vascular morphology suggests that very low concentrations of NO effectively attenuate hypoxic remodeling but that NO is not effective in monocrotaline-induced pulmonary remodeling.

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Crossref · 10.1213/00000539-199801000-00015

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Authors
Horstman, D. J., Frank, D. U., & Rich, G. F.
Affiliations
  • University of Virginia (US)
  • University of Virginia Health System (US)
Corresponding author
Rich, George F.
ORCID
Frank, Deborah U.
Venue
Anesthesia & Analgesia
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1998-01
Volume
86
Issue
1
Pages
74-81
ISSN
0003-2999 (ISSN-L)
DOI
10.1213/00000539-199801000-00015
OpenAlex
W2010517139
Cited by
33
References
26
Citations by year
2019: 2 · 2018: 1 · 2016: 2 · 2012: 1
FWCI
3.20
Type
journal article
Language
en
Open access
closed
Locations
  • Anesthesia & Analgesia (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
  • Health Sciences › Medicine › Genetics › Vascular Anomalies and Treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
Keywords
inhaled nitric oxide, pulmonary vascular remodeling, pulmonary hypertension, hypoxia, monocrotaline, right ventricular hypertrophy, muscular arteries, pulmonary vasodilation, pulmonary vasoconstriction, nitric oxide toxicity, pulmonary vasoactive substances
MeSH terms
Administration, Inhalation, Animals, Hypoxia, Dose-Response Relationship, Drug, Hypertension, Pulmonary, Male, Nitric Oxide, Pulmonary Artery, Monocrotaline, Rats, Sprague-Dawley, Rats

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