Cited by 24Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionCardiovascular, Neuropeptides, and Oxidative Stress Research

Insights into the effect of nitric oxide and its metabolites nitrite and nitrate at inhibiting neointimal hyperplasia

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Vavra, Ashley K., Havelka, George E., Martinez, Janet, Lee, Vanessa R., Fu, Bo, Jiang, Qun, Keefer, Larry K., Kibbe, Melina R.·2011·Nitric Oxide

Abstract

Objective Periadventitial delivery of the nitric oxide (NO) donor PROLI/NO following arterial injury effectively inhibits neointimal hyperplasia. Given the short half-life of NO release from PROLI/NO, our goal was to determine if inhibition of neointimal hyperplasia by PROLI/NO was due to NO, or its metabolites nitrite and nitrate.Methods and results In vitro, the NO donor DETA/NO inhibited proliferation of rat aortic vascular smooth muscle cells (RASMC), but neither nitrite nor nitrate did. In vivo, following rat carotid artery balloon injury or injury plus the molar equivalents of PROLI/NO, nitrite, or nitrate (n=8-11/group), PROLI/NO was found to provide superior inhibition of neointimal hyperplasia (82% inhibition of intimal area, and 44% inhibition of medial area, p<0.001). Only modest inhibition was noted with nitrite or nitrate (45% and 41% inhibition of intimal area, and 31% and 29% inhibition of medial area, respectively, p<0.001). No effects on blood pressure were noted with any treatment groups. In vivo, only PROLI/NO inhibited cellular proliferation and increased arterial lumen area compared to injury alone (p<0.001). However, all three treatments inhibited inflammation (p<0.001).Conclusions PROLI/NO was more effective at inhibiting neointimal hyperplasia following arterial injury than nitrite or nitrate. However, modest inhibition of neointimal hyperplasia was observed with nitrite and nitrate, likely secondary to anti-inflammatory actions. In conclusion, we have demonstrated that the efficacy of NO donors is primarily due to NO production and not its metabolites, nitrite and nitrate.

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Crossref · 10.1016/j.niox.2011.04.013

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Authors
Vavra, A. K., Havelka, G. E., Martinez, J., Lee, V. R., Fu, B., Jiang, Q., Keefer, L. K., & Kibbe, M. R.
Affiliations
  • Northwestern University (US)
  • National Institutes of Health (US)
Corresponding author
Kibbe, Melina R.
Venue
Nitric Oxide
Publisher
Elsevier BV
Published
2011-06
Volume
25
Issue
1
Pages
22-30
ISSN
1089-8603 (ISSN-L)
OpenAlex
W1977833171
Cited by
24
References
40
Citations by year
2026: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2017: 1 · 2016: 3 · 2015: 7 · 2014: 2 · 2013: 1 · 2012: 3
FWCI
1.31
Type
journal article
Language
en
Open access
Locations
  • Nitric Oxide (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Edwards Lifesciences
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (K08HL084203, T32HL094293)
  • Fogarty International Center
  • National Center for Research Resources (UL1RR025741)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
  • Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
Keywords
nitrite, nitrate, intimal hyperplasia, DETA/NO, nitric oxide donors, vascular smooth muscle cell proliferation, balloon injury, carotid artery, anti-inflammatory activity, arterial injury
MeSH terms
Animals, Cells, Cultured, Coronary Artery Disease, Disease Models, Animal, Hyperplasia, Male, Nitrates, Nitric Oxide, Nitrites, Rats, Sprague-Dawley, Cell Proliferation, Rats, Neointima

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