Inhibition of nitric oxide-mediated hypotension and septic shock with iron-containing hemoprotein

DETAILED DESCRIPTION The invention is directed to a method for the prophylaxis or treatment of an animal for systemic hypotension or other pathogenic syndromes induced by inappropriate nitric oxide production.
Such hypotension may be induced by certain cytokines or a microbial toxin such as bacterial endotoxin.
The method involves administering a therapeutically effective amount of an iron hemoprotein such as hemoglobin and the like.
The administration is preferably intravascular, which includes intraarterial and intravenous.
Other parenteral administration routes, e.
g.
peritoneal or intralymphatic, to name but a few, can be used for removal of undesired NO production at related sites.
Enteral administration could be feasible if the hemoprotein or a derivative thereof was resistant to digestion and passed into the circulation.
The animal may be, for example, a domestic mammal or a human patient.
The systemic hypotension most characteristically results from abnormal production of nitric oxide induced by a cytokine or microbial toxin.
A therapeutically effective amount of iron hemoprotein is an amount sufficient to bind and/or oxidize substantially all of the free nitric oxide and thus removing it from the circulation.
In a preferred embodiment, the iron hemoprotein is hemoglobin or myoglobin and is administered intravascularly.
Bacterial endotoxin is a primary causative agent of septic shock.
Elevated levels of nitric oxide have been found in animals in septic shock (Wang et al.
, 1991, Life Sciences 49:55-60).
Therefore, the invention is also directed to a method for the treatment of septic shock in a patient comprising administering a therapeutically effective amount of an iron hemoprotein such as the preferred hemoglobin.