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Ann Allergy Asthma Immunol. 2007 Oct;99(4):306-13.

Role of nitric oxide production in anaphylaxis and its relevance for the treatment of anaphylactic hypotension with methylene blue.

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  • 1Department of Surgery and Anatomy, Ribeirão Preto Faculty of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.



To review the role of nitric oxide production in anaphylaxis.


We performed MEDLINE searches of the literature. In addition, some references known to the authors but not listed in MEDLINE, such as abstracts and a CD-ROM, were included. Finally, additional clinical details of the cases were provided by one of the authors.


Primary reports were preferentially selected for inclusion. However, some secondary publications are also cited.


Histamine along with other mediators, such as leukotrienes, tumor necrosis factor, and platelet-activating factor, induce the production of nitric oxide. Nitric oxide can inhibit the release and effects of catecholamines. Sympathetic amines may inhibit production of nitric oxide. Studies in animals have demonstrated the generation of nitric oxide during anaphylaxis. Inhibition of nitric oxide synthase improves survival in an animal model of anaphylaxis. Nitric oxide causes vasodilation indirectly by increasing the activation of guanylyl cyclase, which then causes smooth muscle relaxation by increasing the concentration of smooth muscle cyclic guanosine monophosphate. Methylene blue is an inhibitor of guanylyl cyclase, which increases systemic vascular resistance and reverses shock in animal studies. The previously reported successful treatment with methylene blue of 11 patients with anaphylactic hypotension is reviewed.


Nitric oxide plays a significant role in the pathophysiology of anaphylaxis. Treatment with methylene blue should be considered in patients with anaphylactic hypotension that has not responded to other interventions.

[PubMed - indexed for MEDLINE]
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