Sodium nitrite therapy attenuates the hypertensive effects of HBOC-201 via nitrite reduction
Open accessAbstract
Hypertension secondary to scavenging of NO remains a limitation in the use of HBOCs (haemoglobin-based oxygen carriers). Recent studies suggest that nitrite reduction to NO by deoxyhaemoglobin supports NO signalling. In the present study we tested whether nitrite would attenuate HBOC-mediated hypertension using HBOC-201 (Biopure), a bovine cross-linked, low-oxygen-affinity haemoglobin. In a similar way to unmodified haemoglobin, deoxygenated HBOC-201 reduced nitrite to NO with rates directly proportional to the extent of deoxygenation. The functional importance of HBOC-201-dependent nitrite reduction was demonstrated using isolated aortic rings and a murine model of trauma, haemorrhage and resuscitation. In the former, HBOC-201 inhibited NO-donor and nitrite-dependent vasodilation when oxygenated. However, deoxygenated HBOC-201 failed to affect nitrite-dependent vasodilation but still inhibited NO-donor dependent vasodilation, consistent with a model in which nitrite-reduction by deoxyHBOC-201 counters NO scavenging. Finally, resuscitation using HBOC-201, after trauma and haemorrhage, resulted in mild hypertension (~5–10 mmHg). Administration of a single bolus nitrite (30–100 nmol) at the onset of HBOC-201 resuscitation prevented hypertension. Nitrite had no effect on mean arterial pressure during resuscitation with LR (lactated Ringer's solution), suggesting a role for nitrite–HBOC reactions in attenuating HBOC-mediated hypertension. Taken together these data support the concept that nitrite can be used as an adjunct therapy to prevent HBOC-dependent hypertension.
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Nitrite therapy can prevent hypertension caused by cell-free hemoglobin-based oxygen carriers in vivo.
“Nitrite reduction to NO by deoxygenated hemoglobin may govern NO signaling in the vasculature as exemplified by experiments showing that nitrite therapy can prevent hypertension induced by cell-free hemoglobin-based oxygen carriers in vivo22.”
From Nitrate and nitrite in biology, nutrition and therapeutics (2009) · cites this paper as [22]
Nitrite reduction to NO by deoxygenated hemoglobin may control NO signaling in the vasculature.
“Nitrite reduction to NO by deoxygenated hemoglobin may govern NO signaling in the vasculature as exemplified by experiments showing that nitrite therapy can prevent hypertension induced by cell-free hemoglobin-based oxygen carriers in vivo22.”
From Nitrate and nitrite in biology, nutrition and therapeutics (2009) · cites this paper as [22]
Doses of ~50 nmoles of nitrite have been shown to be protective in models of ischemia reperfusion and hemorrhagic shock in mice.
“Typically doses of ~50 nmoles have been shown to be protective in models of ischemia reperfusion [52, 114] as well hemorrhagic shock in mice [122] for example.”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [122]
Relatively low doses of nitrite are sufficient to induce dramatic protective effects in vivo.
“experimental observations show that relatively low doses of nitrite are sufficient to induce dramatic protective effects in vivo.”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [122]
Administration of bolus nitrite (30-100 nmol) at the onset of hemoglobin-based oxygen carriers (HBOC-201) resuscitation prevents hypertension.
“In a study by Rodriguez et al it was reported that administration of bolus nitrite (30–100 nmol) at the onset of hemoglobin based oxygen carriers (HBOC-201) resuscitation prevented hypertension [198].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [198]
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References 52 · Cited by 31
- Authors
- Rodriguez, C., Vitturi, D. A., He, J., Vandromme, M., Brandon, A., Hutchings, A., Rue, L. W., Kerby, J. D., & Patel, R. P.
- Affiliations
- University of Alabama at Birmingham (US)
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A.
- Corresponding author
- Rodriguez, Cilina
- He, Jin
- Vandromme, Marianne
- Hutchings, Anne
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2009-08-27
- Volume
- 422
- Issue
- 3
- Pages
- 423-432
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC2775055
- OpenAlex
- W2089334038
- Cited by
- 31
- References
- 52
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 6 · 2012: 3
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical Journal (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (T32GM063490)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
- Keywords
- HBOC-201, hemoglobin-based oxygen carriers, nitrite reduction, nitric oxide scavenging, deoxyhemoglobin, aortic rings, nitric oxide signaling
- MeSH terms
- Animals, Antihypertensive Agents, Aorta, Blood Substitutes, Disease Models, Animal, Hemoglobins, Hypertension, Male, Mice, Inbred C57BL, Nitric Oxide, Nitrite Reductases, Sodium Nitrite, Vasodilation, Rats, Sprague-Dawley, Nitric Oxide Donors, Mice, Rats
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