Insights into the effect of nitric oxide and its metabolites nitrite and nitrate at inhibiting neointimal hyperplasia
Open accessAbstract
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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Dietary nitrate and nitrite confer protection from intimal hyperplasia in rodents.
“Further, dietary nitrate and nitrite confer protection from intimal hyperplasia in rodents[117–119]”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [119]
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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)
- PMC
- PMC3119546
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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