Sodium nitrite therapy attenuates the hypertensive effects of HBOC-201 via nitrite reduction.

Abstract

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 ( approximately 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.

• Authors: Cilina Rodriguez, Dario A Vitturi, Jin He, Marianne Vandromme, Angela Brandon, Anne Hutchings, Loring W Rue 3rd, Jeffrey D Kerby, Rakesh P Patel
• Journal: The Biochemical journal (Biochem J) Vol. 422 Issue 3 Pg. 423-32 (Aug 27 2009) ISSN: 1470-8728 [Electronic] England
• PMID: 19555351 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antihypertensive Agents
• Blood Substitutes
• Hemoglobins
• Nitric Oxide Donors
• HBOC 201
• Nitric Oxide
• deoxyhemoglobin
• Nitrite Reductases
• Sodium Nitrite

Topics

• Animals
• Antihypertensive Agents (pharmacology, therapeutic use)
• Aorta (drug effects)
• Blood Substitutes (metabolism, pharmacology)
• Disease Models, Animal
• Hemoglobins (metabolism, pharmacology)
• Hypertension (drug therapy)
• Male
• Mice
• Mice, Inbred C57BL
• Nitric Oxide (metabolism)
• Nitric Oxide Donors (pharmacology)
• Nitrite Reductases (metabolism)
• Rats
• Rats, Sprague-Dawley
• Sodium Nitrite (pharmacology, therapeutic use)
• Vasodilation (drug effects)