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Restraint Stress-Induced Expression of Fos and Several Related Genes in the Hypothalamus of Hypertensive ISIAH Rats

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Abstract

Stress can play a significant role in arterial hypertension and many other complications of cardiovascular diseases. Considerable attention is paid to the study of the molecular mechanisms involved in the body response to stressful influences, but there are still many blank spots in understanding the details. ISIAH rats model the stress-sensitive form of arterial hypertension. ISIAH rats are characterized by genetically determined enhanced activities of the hypothalamic–pituitary–adrenocortical and sympathetic–adrenomedullary systems, suggesting a functional state of increased stress reactivity. For the first time, the temporal expression patterns of Fos and several related genes were studied in the hypothalamus of adult male hypertensive ISIAH rats after a single exposure to restraint stress for 30, 60, or 120 min. Fos transcription was activated and peaked 1 h after the start of restraint stress. The time course of Fos activation coincided with that of blood pressure increase after stress. Activation of hypothalamic neurons also alters the transcription levels of several transcription factor genes (Jun, Nr4a3, Jdp2, and Ppargc1a), which are associated with the development of cardiovascular diseases. Because Fos induction is a marker of brain neuron activation, activation of hypothalamic neurons and an increase in blood pressure were concluded to accompany increased stress reactivity of the hypothalamic–pituitary–adrenocortical and sympathoadrenal systems in hypertensive ISIAH rats during short-term restraint.

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ACKNOWLEDGMENTS

We are grateful to staff of the conventional breeding facility of the Center of Genetic Resources of Laboratory Animals (Institute of Cytology and Genetics, Novosibirsk, Russia) for rearing experimental rats for Russian governmental project no. FWNR-2022-0008 and the Joint Center of Genome Studies (Institute of Cytology and Genetics, project no. FWNR-2022-0017) for the opportunity to use their equipment for qualitative and quantitative nucleic acid testing.

Funding

This work was supported by the Russian Science Foundation (project no. 22-14-00082).

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Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

    Y. V. Makovka, L. A. Fedoseeva, D. Yu. Oshchepkov, A. L. Markel & O. E. Redina

  2. Novosibirsk State University, 630090, Novosibirsk, Russia

    Y. V. Makovka & A. L. Markel

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  1. Y. V. Makovka
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  2. L. A. Fedoseeva
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  3. D. Yu. Oshchepkov
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Correspondence to Y. V. Makovka.

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CONFLICT OF INTEREST

The authors of this work declare that they have no conflicts of interest.

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

All procedures were performed in compliance with international rules for studies with animals. The study protocol was approved by the Bioethical Council of the Federal Research Center Institute of Cytology and Genetics SB RAS (Novosibirsk, Russia), Protocol no. 115 dated December 20, 2021.

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Translated by T. Tkacheva

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Abbreviations: ISIAH, inherited stress-induced arterial hypertension; WAG, Wistar Albino Glaxo; BP, blood pressure; qPCR, quantitative (real-time) polymerase chain reaction; ACTH, adrenocorticotropic hormone.

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Makovka, Y.V., Fedoseeva, L.A., Oshchepkov, D.Y. et al. Restraint Stress-Induced Expression of Fos and Several Related Genes in the Hypothalamus of Hypertensive ISIAH Rats. Mol Biol 58, 62–70 (2024). https://doi.org/10.1134/S0026893324010072

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