Skip to main content
Download PDF

Blocking soluble guanylate cyclase could be the present and future of NO/cGMP inhibition for vasoplegia treatment

Critical Care volume 22, Article number: 104 (2018) Cite this article

The Original Article was published on 27 February 2018

Cumulative evidence indicates that NO/cGMP inhibition would make a difference in vasoplegia treatment. Unfortunately, methylene blue (MB) is the only compound we currently have that can be used for this purpose. The effects of MB are apparent only in the case of nitric oxide (NO) up-regulation, and it is not a vasoconstrictor per se. Blocking the cGMP system “releases” the cAMP system in a kind of “crosstalk,” facilitating the noradrenaline vasoconstrictor effect [1, 2].

I recently wrote an editorial opinion suggesting this approach as an unexplored therapeutic frontier for the pharmaceutical industry. MB is the oldest drug infused in humans, is cheap, and is not patented for industrial use, but the medical literature insists that it has not been the subject of any sizeable clinical trials, even considering its safety at low doses. However, it is mandatory to use it early, not as rescue therapy [3].

Studies suggest that MB has a potential role in protecting the microcirculation. In an experimentally induced septic shock model in rats, only the combination of norepinephrine (NE) and MB restored mean arterial pressure to control levels by the end of the 3-h experiment. Intravital microscopy demonstrated better microvascular integrity in the presence of MB, and severe damage to animals that were infused with only NE [4]. Therefore, MB would be an option to prevent direct organ damage from adrenergic agents.

Levy and colleagues wrote an excellent review article about the “past, present and future” of vasoplegia treatment and presented some concerns about MB use [5]. Not considering MB itself, blocking soluble guanylate cyclase (sGC), the final NO/cGMP messenger, in smooth muscle is underestimated and deserves a place in the present and future.

Abbreviations

cAMP:

Cyclic adenosine monophosphate

cGMP:

Cyclic guanosine monophosphate

MB:

Methylene blue

NO:

Nitric oxide

References

  1. Evora PR, Ribeiro PJ, Vicente WV, Reis CL, Rodrigues AJ, Menardi AC, Alves Junior L, Evora PM, Bassetto S. Methylene blue for vasoplegic syndrome treatment in heart surgery: fifteen years of questions, answers, doubts and certainties. Rev Bras Cir Cardiovasc. 2009;24(3):279–88.

    Article  PubMed  Google Scholar 

  2. Evora PR, Alves Junior L, Ferreira CA, Menardi AC, Bassetto S, Rodrigues AJ, Scorzoni Filho A, Vicente WV. Twenty years of vasoplegic syndrome treatment in heart surgery. Methylene blue revised. Rev Bras Cir Cardiovasc. 2015;30(1):84–92.

    PubMed  PubMed Central  Google Scholar 

  3. Evora PRB. G-proteins agonists and NO/cGMP blockers: unexplored frontiers in the pharmaceutical industry. Arq Bras Cardiol. 2017 Oct;109(4):275–6.

    PubMed  PubMed Central  Google Scholar 

  4. Nantais J, Dumbarton TC, Farah N, Maxan A, Zhou J, Minor S, Lehmann C. Impact of methylene blue in addition to norepinephrine on the intestinal microcirculation in experimental septic shock. Clin Hemorheol Microcirc. 2014;58(1):97–105.

    PubMed  Google Scholar 

  5. Levy B, Fritz C, Tahon E, Jacquot A, Auchet T, Kimmoun A. Vasoplegia treatments: the past, the present, and the future. Crit Care. 2018;22(1):52.

    Article  PubMed  Google Scholar 

Download references

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author information

Authors and Affiliations

  1. Department of Surgery and Anatomy (Division of Cardiothoracic Surgery); Ribeirão Preto School of Medicine, University of São Paulo, Rua Rui Barbosa, 367, Ap 15, Rbeirão Preto, SP, 14015-120, Brazil

    Paulo Roberto Barbosa Evora

Authors
  1. Paulo Roberto Barbosa Evora
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PRBE contributed to the study concept and design and read and approved the final manuscript.

Corresponding author

Correspondence to Paulo Roberto Barbosa Evora.

Ethics declarations

Competing interests

The author declares that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Additional information

See related research by Levy et al., https://ccforum.biomedcentral.com/articles/10.1186/s13054-018-1967-3

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Barbosa Evora, P.R. Blocking soluble guanylate cyclase could be the present and future of NO/cGMP inhibition for vasoplegia treatment. Crit Care 22, 104 (2018). https://doi.org/10.1186/s13054-018-2024-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13054-018-2024-y

Critical Care

ISSN: 1364-8535