Sodium nitrite therapy attenuates the hypertensive effects of HBOC-201 via nitrite reduction.
Biochem J
; 422(3): 423-32, 2009 Aug 27.
Article
em En
| MEDLINE
| ID: mdl-19555351
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nitrito de Sódio
/
Substitutos Sanguíneos
/
Hemoglobinas
/
Hipertensão
/
Anti-Hipertensivos
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article