Effect of subchronic use of unsymmetrical dimethylhydrazine on contractile activity of isolated lymphatic vessels

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Abstract

Introduction. Unsymmetric dimethylhydrazine (UDMH, heptyl) is widely used as a rocket fuel. Heptyl belongs to especially dangerous substances (hazard class I). UDMH with chronic intragastric administration has a cardiotropic effect, which served as the basis for studying its effect on the contractile activity of lymphatic vessels, since they are part of the vascular system. In addition, lymphatic vessels are considered as objects similar in terms of parameters of phase contractile activity with the heart and having a certain commonality of regulatory mechanisms of cardiomyocytes and smooth muscle cells of lymphangions.

Materials and methods. The toxic effect of UDMH was evaluated on a model of isolated rat lymphatic vessels with subchronic intragastric administration of heptyl for 28 days at doses of 0.02; 0.2; and 2 mg/kg.

Results. The use of UDMH in all studied doses led to a decrease in the contractile activity of lymphatic vessels, which manifested itself in the suppression of the frequency and amplitude of contractions and, as a consequence, the integral indicator – minute productivity. At the same time, the tonic voltage increased dose-dependent. When assessing the state of the endothelium of lymphatic vessels using acetylcholine, a decrease (inversion) of the response of lymphangions to the vasodilator was revealed.

Limitations of the study. The study was performed on male white rats and does not take into account gender differences in the effect of NDMG on lymphatic vessels.

Conclusion. As a result of the study, it was found that UDMH in doses of 0.02; 0.2; and 2 mg/kg causes inhibition of the pumping function of lymphatic vessels, due to a violation of the processes of both excitation and contraction in smooth muscle cells of lymphangions.

Compliance with ethical standards. The study was carried out in accordance with the rules of bioethics approved by the European Convention for the Protection of Vertebrates Used for Experimental and Other Purposes and approved by the Local Bioethical Commission of FSUE "Scientific Research Institute GPECH" of the FMBA of Russia.

Contribution of authors:
Nechaykina O.V. — concept and design of the study, collection and processing of material, writing of text;
Petunov S.G. — concept and design of the study, editing;
Laptev D.S. — concept and design of research, editing;
Bobkov D.V. — editing.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Conflict of interest. The authors declare that there is no conflict of interest.

Acknowledgment. The study was carried out within the framework of the implementation of the state program of the Russian Federation “Development of healthcare”.

Received: August 30, 2023 / Revised: November 1, 2023 / Accepted: December 28, 2023 / Published: February  29, 202

 

About the authors

Olga V. Nechaykina

Research Institute of Hygiene, Occupational Pathology and Human Ecology, FMBA

Author for correspondence.
Email: olga2278@mail.ru
ORCID iD: 0000-0001-7151-7240

Senior Researcher at the Laboratory of Extreme Physiology of the Research Institute of Hygiene, Occupational Pathology and Human Ecology of the Federal medical and biological Agency, 188663, Leningrad region, RF

e-mail: olga2278@mail.ru

Russian Federation

Sergey G. Petunov

Research Institute of Hygiene, Occupational Pathology and Human Ecology, FMBA

Email: sergey-petunov@mail.ru
ORCID iD: 0000-0001-6781-8315

Candidate of Medical Sciences, Associate Professor, Head of the Scientific and Organizational Department of the Research Institute of Hygiene, Occupational Pathology and Human Ecology of the Federal medical and biological Agency, 188663, Leningrad region, RF

e-mail: sergey-petunov@mail.ru

Russian Federation

Denis S. Laptev

Research Institute of Hygiene, Occupational Pathology and Human Ecology, FMBA

Email: lapden@mail.ru
ORCID iD: 0000-0002-3960-3058

Candidate of Biological Sciences, Head of the Laboratory of Extreme Physiology of the Research Institute of Hygiene, Occupational Pathology and Human Ecology of the Federal medical and biological Agency, 188663, Leningrad region, RF

e-mail: lapden@mail.ru

Russian Federation

Dmitry V. Bobkov

Research Institute of Hygiene, Occupational Pathology and Human Ecology, FMBA

Email: bdv21@yandex.ru
ORCID iD: 0000-0003-3989-0437

Senior Researcher at the Laboratory of Extreme Physiology of the Research Institute of Hygiene, Occupational Pathology and Human Ecology of the Federal medical and biological Agency, 188663, Leningrad region, Russian Federation

e-mail: bdv21@yandex.ru

Russian Federation

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