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What Is the Reason that Gaseous Nitric Oxide Inhalation Does Not Affect Systemic Arterial Pressure in Humans and Animals?

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Abstract

The reason for the lack of the hypotensive effect of gaseous NO, as introduced by inhalation into the bodies of animals and humans, has been identified. Since this defect was completely eliminated by inhalation of NO simultaneous with intravenous administration of low molecular mass thiol solutions to animals (rats), it is concluded that gaseous NO entering through the lungs into the blood circulating in a large circle of blood circulation converts into nitrosonium cation (NO+) as a result of single-electron oxidation, which is unable to exert vasodilating and thereby hypotensive effects on animals and humans. The binding of NO+ to low molecular mass thiols leads to its transformation into S-nitrosothiols, followed by the release of this nitrosyl agent in the form of neutral NO molecules characterized by hypotensive activity. The formation of dinitrosyl iron complexes with thiol-containing ligands in the blood and tissues of organs of experimental animals in these experiments, which could cause a hypotensive effect, was not detected. The hypotensive effect of inhaled NO, which was found in the lungs, could be due to the penetration of NO through the outer wall of blood vessels with subsequent activation of the enzyme guanylate cyclase, an inducer of vasodilation and hypotension, directly in the walls of blood vessels.

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Funding

The work was carried out with the financial support of the Russian Science Foundation, project no. 23-74-00009.

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Authors and Affiliations

  1. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, 119334, Moscow, Russia

    A. F. Vanin

  2. Chazov National Medical Research Center of Cardiology, Ministry of Health of the Russian Federation, 121552, Moscow, Russia

    A. A. Abramov, A. A. Timoshin, V. L. Lakomkin & E. K. Ruuge

  3. Bauman Moscow State Technical University, 105005, Moscow, Russia

    A. B. Vagapov & A. V. Pekshev

Authors
  1. A. F. Vanin
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  2. A. A. Abramov
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  3. A. B. Vagapov
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  4. A. A. Timoshin
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  5. A. V. Pekshev
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  6. V. L. Lakomkin
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  7. E. K. Ruuge
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Corresponding author

Correspondence to A. F. Vanin.

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CONFLICT OF INTEREST

The authors declare that they have no conflicts of interest.

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

Experiments with rats were conducted in strict accordance with the legislation of the Russian Federation and the provisions of the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (Strasbourg, March 18, 1986). The provisions of the Guidelines on the Care and Use of Laboratory Animals (Washington, D.C., 2011) and other norms of international law governing the maintenance and use of laboratory animals from the point of view of humane treatment of animals and their rational use were strictly observed. The experimental protocol of the study was approved by the Bioethics Commission of the Chazov National Medical Research Center of Cardiology, Ministry of Health of the Russian Federation (registration number of the meeting protocol no. LEPS/18.07.23 dated July 18, 2023).

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Translated by E. Puchkov

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Abbreviations: ABP, average blood pressure; DNIC-TCL, dinitrosyl iron complexes with thiol-containing ligands; M-DNIC, mononuclear form of dinitrosyl iron complexes; B-DNIC, binuclear form of dinitrosyl iron complexes.

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Vanin, A.F., Abramov, A.A., Vagapov, A.B. et al. What Is the Reason that Gaseous Nitric Oxide Inhalation Does Not Affect Systemic Arterial Pressure in Humans and Animals?. BIOPHYSICS 68, 1048–1052 (2023). https://doi.org/10.1134/S0006350923060209

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  • DOI: https://doi.org/10.1134/S0006350923060209

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