Nitrite Attenuates Ischemia-Reperfusion–Induced Microcirculatory Alterations and Mitochondrial Dysfunction in the Microvasculature of Skeletal Muscle
Abstract
BACKGROUND: Recently, nitrite has been rediscovered as a physiologically relevant storage reservoir of nitric oxide in blood and it can readily be converted to nitric oxide under hypoxic and acidic conditions. In this study, the authors evaluated the therapeutic efficacy of nitrite on reperfusion-induced microcirculatory alterations and mitochondrial dysfunction in the microvasculature of skeletal muscle. METHODS: The authors used a vascular pedicle isolated rat cremaster model that underwent 4 hours of warm ischemia followed by 2 hours or 17 hours of reperfusion. At 5 minutes before reperfusion, normal saline, sodium nitrite (0.20 μM/minute/kg), or nitrite mixed with 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl (potassium salt) (0.2 mg/minute/kg) was infused into the microcirculation of ischemic cremaster by means of intraarterial infusion. Ischemia-reperfusion-induced microcirculatory alterations were measured after 2 hours of reperfusion. Microvasculature of the cremaster muscle including the vascular pedicle was harvested to determine the mitochondrial dysfunction. The blood concentration of methemoglobin was also measured to determine the toxicity of nitrite. RESULTS: The authors found that nitrite significantly attenuated ischemia-reperfusion-induced vasoconstriction, arteriole stagnation, and capillary no-reflow in the early phase of reperfusion and the depolarization of mitochondrial membrane potential and cytochrome c release in the late phase of reperfusion. Nitrite-induced protection was significantly blocked by a nitric oxide scavenger (potassium salt). The methemoglobin results showed that the doses of nitrite we used in the present study were safe. CONCLUSION: The supplementation of a low dose of nitrite, directly into the microcirculation of ischemic muscle through local intraarterial infusion, significantly attenuated ischemia-reperfusion-induced microcirculatory alterations in vivo and mitochondrial dysfunction in vitro in the microvasculature of skeletal muscle.
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Nitrite is protective against ischemia/reperfusion and other forms of injury in multiple tissues and organs.
“Numerous investigations have reported that nitrite is protective against I/R and other forms of injury in multiple tissues and organs (81, 125, 188), as reviewed extensively elsewhere (157).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [188]
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Widgerow, A. D. (2012) · Annals of Plastic Surgery · doi:10.1097/sap.0b013e31825c089c · Cited by 70 · see citing works
“- low doses of sodium nitrite directly into the microcirculation of ischemic muscle through intra-arterial infusion.(6,22) - preischemic delivery of hydrogen sulfide or Diannexin,(9) ad-”
BackgroundInorganic nitrite supplementation for healthy arterial aging
Sindler, A. L., DeVan, A. E., Fleenor, B. S., & Seals, D. R. (2014) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01100.2013 · Cited by 68 · see citing works
Rassaf, T., Ferdinandy, P., & Schulz, R. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12291 · Cited by 62 · see citing works
“The supplementation of a low dose of nitrite through local intra-arterial infusion, attenuated ischaemiareperfusion-induced vasoconstriction, arteriole stagnation, and capillary no-reflow during reperfusion (Wang et al., 2011) and prolonged application of nitrite improved revascularization in chronically ischaemic per…”
BackgroundTherapeutic Interventions Against Reperfusion Injury in Skeletal Muscle
Wang, W. Z., Baynosa, R. C., & Zamboni, W. A. (2011) · Journal of Surgical Research · doi:10.1016/j.jss.2011.07.015 · Cited by 45 · see citing works
Self-citationDonnarumma, E., Bhushan, S., Bradley, J., Otsuka, H., Donnelly, E. L., Lefer, D. J., & Islam, K. N. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.116.003551 · Cited by 42 · see citing works
Adipose-Derived Stem Cells Ameliorate Ischemia-Reperfusion Injury in a Rat Skin Free Flap Model
Casado, J. G., Abellán, E., Vela, F. J., et al. (2018) · Journal of Reconstructive Microsurgery · doi:10.1055/s-0038-1648246 · Cited by 16 · see citing works
The macrophage stimulating anti-cancer agent, RRx-001, protects against ischemia-reperfusion injury
Cabrales, P., Caroen, S. Z., Oronsky, A. L., Carter, C. A., Trepel, J. B., Summers, T. A., Reid, T. R., Oronsky, N. C., Lybeck, M., & Oronsky, B. T. (2017) · Expert Review of Hematology · doi:10.1080/17474086.2017.1324779 · Cited by 15 · see citing works
“In skeletal I/R Wang et al and Murata et al demonstrated that low dose nitrite significantly attenuated vasoconstriction, arteriole stagnation, and capillary no-reflow.(14,15) In brain I/R, nitrite was neuroprotective(16) and Campelo et al demonstrated that NO release improved total brain infarction area and hippocamp…”
BackgroundWang, W. Z., Fang, X., Williams, S., et al. (2015) · Plastic & Reconstructive Surgery · doi:10.1097/prs.0000000000001097 · Cited by 7 · see citing works
Self-citationEngel, H., Friedrich, S., Schleich, C., et al. (2014) · Annals of Plastic Surgery · doi:10.1097/sap.0000000000000148 · Cited by 7 · see citing works
“addressed some of these questions and could demonstrate attenuated IRI via local intra-arterial nitrite infusion.(18)”
BackgroundGazyakan, E., Hirche, C. R., Reichenberger, M. A., et al. (2020) · Journal of Plastic Reconstructive & Aesthetic Surgery · doi:10.1016/j.bjps.2020.08.021 · Cited by 5 · see citing works
Nitrate and Nitrite in Aging and Age-Related Disease
Johnson, L. C., DeVan, A. E., Justice, J. N., & Seals, D. R. (2017) · Springer eBooks · doi:10.1007/978-3-319-46189-2_18 · Cited by 5 · see citing works
Pharmaceutical Preconditioning With Nitric Oxide Synthase and l-Arginine in Ischemic Tissues
Gazyakan, E., Hirche, C. R., Reichenberger, M. A., Germann, G., & Engel, H. (2019) · Annals of Plastic Surgery · doi:10.1097/sap.0000000000002117 · Cited by 5 · see citing works
Wang, W. Z. (2016) · Plastic & Reconstructive Surgery Global Open · doi:10.1097/gox.0000000000001067 · Cited by 3 · see citing works
Self-citationSíndrome de isquemia-reperfusión en microcirugía
Gonzalez, T. G., Nieto, L. E., & Cardona, D. (2023) · Universitas Médica · doi:10.11144/javeriana.umed64-1.isqu
- Authors
- Wang, W. Z., Fang, X.-H., Stephenson, L. L., Zhang, X., Williams, S. J., Baynosa, R. C., Khiabani, K. T., & Zamboni, W. A.
- Affiliations
- University of Nevada, Las Vegas (US)
- University of Nevada, Reno (US)
- Venue
- Plastic and Reconstructive Surgery
- Published
- 2011-10
- Volume
- 128
- Issue
- 4
- Pages
- 279e-287e
- ISSN
- 0032-1052 (ISSN-L)
- OpenAlex
- W2313018523
- Cited by
- 14
- References
- 0
- Citations by year
- 2023: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Plastic & Reconstructive Surgery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- nitrite, sodium nitrite, ischemia-reperfusion injury, microcirculation, mitochondrial dysfunction, skeletal muscle, nitric oxide, vasoconstriction, mitochondrial membrane potential, cytochrome c release, methemoglobin, cremaster muscle, intra-arterial infusion, nitric oxide scavengers
- MeSH terms
- Analysis of Variance, Animals, Disease Models, Animal, Dose-Response Relationship, Drug, Ischemia, Male, Membrane Potentials, Methemoglobin, Microcirculation, Mitochondria, Muscle, Nitrites, Random Allocation, Reference Values, Reperfusion Injury, Rats, Sprague-Dawley, Muscle, Skeletal, Cytochromes c, Rats
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