The role of vascular myoglobin in nitrite-mediated blood vessel relaxation
Open accessAbstract
AIMS: This work investigates the role of myoglobin in mediating the vascular relaxation induced by nitrite. Nitrite, previously considered an inert by-product of nitric oxide metabolism, is now believed to play an important role in several areas of pharmacology and physiology. Myoglobin can act as a nitrite reductase in the heart, where it is plentiful, but it is present at a far lower level in vascular smooth muscle-indeed, its existence in the vessel wall is controversial. Haem proteins have been postulated to be important in nitrite-induced vasodilation, but the specific role of myoglobin is unknown. The current study was designed to confirm the presence of myoglobin in murine aortic tissue and to test the hypothesis that vascular wall myoglobin is important for nitrite-induced vasodilation. METHODS AND RESULTS: Aortic rings from wild-type and myoglobin knockout mice were challenged with nitrite, before and after exposure to the haem-protein inhibitor carbon monoxide (CO). CO inhibited vasodilation in wild-type rings but not in myoglobin-deficient rings. Restitution of myoglobin using a genetically modified adenovirus both increased vasodilation to nitrite and reinstated the wild-type pattern of response to CO. CONCLUSION: Myoglobin is present in the murine vasculature and contributes significantly to nitrite-induced vasodilation.
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Under anoxic conditions, nitrite-mediated vasodilation in murine aortic rings is reduced by CO in wild type mice but not in myoglobin knockout mice.
“Using murine aortic rings under anoxic conditions, Ormerod and coworkers showed that nitrite-mediated vasodilation is reduced by CO (presumably due to blockage of the heme) for wild type but not myoglobin knockout mice [113].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [113]
Smooth muscle myoglobin is implicated in modulating nitrite-dependent increases in blood flow.
“Smooth muscle myoglobin has also been implicated in modulating nitrite-dependent increases in blood flow [56, 113].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [113]
The remainder of the nitrite-mediated effects in the Ormerod study were attributed to XOR and SO based on inhibitor use.
“The remainder of the nitrite mediated effects were attributed to XOR and SO based on use of inhibitors [113].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [113]
Myoglobin serves as an important reductase during tissue ischemia.
“Recent work from several laboratories indicates that myoglobin serves as an important reductase during tissue ischemia [111, 112].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [112]
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- Authors
- Ormerod, J. O. M., Ashrafian, H., Maher, A. R., Arif, S., Steeples, V., Born, G. V. R., Egginton, S., Feelisch, M., Watkins, H., & Frenneaux, M. P.
- Affiliations
- University of Birmingham (GB)
- University of Oxford (GB)
- University of London (GB)
- University of Warwick (GB)
- University of Aberdeen (GB)
- Corresponding author
- Frenneaux, M. P.
- Venue
- Cardiovascular Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-10-01
- Volume
- 89
- Issue
- 3
- Pages
- 560-565
- ISSN
- 0008-6363 (ISSN-L)
- PMC
- PMC3028970
- OpenAlex
- W2103285852
- Cited by
- 61
- References
- 36
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 14 · 2013: 6 · 2012: 15
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Cardiovascular Research (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Wellcome Trust (090532)
- British Heart Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Keywords
- nitrite, nitrite reductase, carbon monoxide, haem proteins, aortic smooth muscle, adenoviral gene transfer, nitric oxide metabolism
- MeSH terms
- Animals, Aorta, Carbon Monoxide, Drug Interactions, Male, Muscle, Smooth, Vascular, Myoglobin, Nitric Oxide, Nitrite Reductases, Nitrites, Nitroprusside, Vasodilation, Mice, Knockout, Nitric Oxide Donors, Mice
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