Effect of Nitric Oxide Pathway Inhibition on the Evolution of Anaphylactic Shock in Animal Models: A Systematic Review

Maryam Alfalasi, Sarah Alzaabi, Linda Östlundh, Rami H. Al-Rifai, Suhail Al-Salam, Paul Michel Mertes, Seth L. Alper, Elhadi H. Aburawi, Abdelouahab Bellou

Research output: Contribution to journalReview articlepeer-review


Nitric oxide (NO) induces vasodilation in various types of shock. The effect of pharmaco-logical modulation of the NO pathway in anaphylactic shock (AS) remains poorly understood. Our objective was to assess, through a systematic review, whether inhibition of NO pathways (INOP) was beneficial for the prevention and/or treatment of AS. A predesigned protocol for this systematic review was published in PROSPERO (CRD42019132273). A systematic literature search was conducted till March 2022 in the electronic databases PubMed, EMBASE, Scopus, Cochrane and Web of Science. Heterogeneity of the studies did not allow meta-analysis. Nine hundred ninety unique studies were identified. Of 135 studies screened in full text, 17 were included in the review. Among six inhibitors of NO pathways identified, four blocked NO synthase activity and two blocked guanylate cyclase downstream activity. Pre-treatment was used in nine studies and post-treatment in three studies. Five studies included both pre-treatment and post-treatment models. Overall, seven pre-treatment studies from fourteen showed improvement of survival and/or arterial blood pressure. Four post-treatment studies from eight showed positive outcomes. Overall, there was no strong evidence to conclude that isolated blockade of the NO/cGMP pathway is sufficient to prevent or restore anaphylactic hypotension. Further studies are needed to analyze the effect of drug combinations in the treatment of AS.

Original languageEnglish
Article number919
Issue number6
Publication statusPublished - Jun 2022


  • anaphylactic shock
  • cyclic guanosine monophosphate
  • guanylate cyclase
  • nitric oxide
  • nitric oxide synthase

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Agricultural and Biological Sciences


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