Dose-Dependent Mechanisms of Melatonin on the Functioning of the Cardiovascular System and on the Behavior of Normotensive Rats of Different Ages
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The purpose of the work on normotensive rats of different age groups (3, 15, and 22 months) is to study the synchronism between the functioning of the cardiovascular system and the locomotor activity of animals in open field tests by a single injection of exogenous melatonin in different doses (1 and 10 mg/kg). The studies show a unidirectional dose-dependent effect of exogenous melatonin on the locomotor activity of rats of different ages and an age-dependent effect of melatonin on the parameters of the cardiovascular system. The results show the possible desynchronization between the circadian rhythms of locomotor activity and the functioning of the cardiovascular system with aging, which can lead to a discrepancy between hemodynamic parameters and the level of locomotor activity.
Keywords:melatonin circadian rhythm cardiovascular system heart rate variability open field test
COMPLIANCE WITH ETHICAL STANDARDS
Conflict of interest. The authors delate that they have no conflict of interest.
Statement on the welfare of animals. The conditions of the research were in accordance with the ethical standards of the Almazov National Medical Research Centre (St. Petersburg), European Communities Council Directive 1986 (86/609/ EEC), and the rules stated in the Guide for the Care and Use of Laboratory Animals.
This study does not contain any studies involving human participants performed by any of the authors.
- 1.Anisimov, V.N., Epiphysis, biorhythms, and aging of an organism, Usp. Fiziol. Nauk, 2008, vol. 39, no. 4, pp. 40–65.Google Scholar
- 2.Arushanyan, E.B. and Popov, A.V., Modern concepts on the role of the suprachiasmatic nuclei of the hypothalamus in the organization of diurnal periodism of physiological functions, Usp. Fiziol. Nauk, 2011, vol. 42, no. 4, pp. 39–58.Google Scholar
- 3.Beier, E.V. and Skornyakov, A.A., Comparative assessment of psychotropic activity of melatonin on various behavioral models, Trudy X Mezhdunarodnogo kongressa “Zdorov’e i obrazovanie XXI veka” (Proc. X Int. Congr. “Health and Education in 21st Century”), Moscow, 2011, vol. 13, no. 7, p. 319.Google Scholar
- 4.Beier, E.V., Skornyakov, A.A., and Arushanyan, E.B., Effect of pineal gland removal on the psychotropic activity of adaptogenic agents in rats, Med. Vestn. Sev. Kavk., 2014, vol. 9, no. 3, pp. 254–258.Google Scholar
- 6.Kurbatova, I.V., Topchieva, L.V., and Nemov, N.N., Circadian genes and cardiovascular pathologies, Tr. Karel. Nauchn. Tsentra, Ross. Akad. Nauk, 2014, no. 5, pp. 3–17.Google Scholar
- 7.American Heart Association, Heart rate variability: standards of measurement, physiological interpretation, and clinical use, Circulation, 1996, vol. 93, no. 5, pp. 1043–1065.Google Scholar
- 8.Acuña-Castroviejo, D., Escames, G., Venegas, C., et al., Extra pineal melatonin: sources, regulation, and potential functions, Cell Mol. Life Sci., 2014, vol. 71, no. 16, pp. 2997–3025.Google Scholar
- 9.Adamsson, M., Laike, T., and Morita, T., Annual variation in daily light exposure and circadian change of melatonin and cortisol concentrations at a northern latitude with large seasonal differences in photoperiod length, J. Physiol. Anthropol., 2016, vol. 36, no. 1, p. 6. https://doi.org/10.1186/s40101-016-0103-9 CrossRefGoogle Scholar
- 12.Benloucif, S., Masana, M.I., and Dubocovich, M.L., Responsiveness to melatonin and its receptor expression in the aging circadian clock of mice, Am. J. Physiol., 1997, vol. 273, no. 6, pp. R1855– R1860.Google Scholar
- 14.Campos Costa, I., Nogueira Carvalho, H., and Fernandes, L., Aging, circadian rhythms and depressive disorders: a review, Am. J. Neurodegener. Dis., 2013, vol. 2, no. 4, pp. 228–246.Google Scholar
- 22.Gupta, A.K., Cornelissen, G., Greenway, F.L., et al., Abnormalities in circadian blood pressure variability and endothelial function: pragmatic markers for adverse cardiometabolic profiles in asymptomatic obeseadults, Cardiovasc. Diabetol., 2010, vol. 9, p. 58. https://doi.org/10.1186/1475-2840-9-58 CrossRefGoogle Scholar
- 23.Grossman, E., Laudon, M., and Zisapel, N., Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials, Vasc. Health Risk Manage., 2011, vol. 7, pp. 577–584.Google Scholar
- 26.Huang, L., Zhang, C., Hou, Y., et al., Blood pressure reducing effects of piromelatine and melatonin in spontaneously hypertensive rats, Eur. Rev. Med. Pharmacol. Sci., 2013, vol. 17, no. 18, pp. 2449–2456.Google Scholar
- 27.Hutchinson, A.J., Hudson, R.L., and Dubocovich, M.L., Genetic deletion of MT(1) and MT(2) melatonin receptors differentially abrogates the development and expression of methamphetamine-induced locomotor sensitization during the day and the night in C3H/HeN mice, J. Pineal Res., 2012, vol. 53, no. 4, pp. 399–409.CrossRefGoogle Scholar
- 28.Jenwitheesuk, A., Boontem, P., Wongchitrat, P., et al., Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-FOXO1 pathway, EXCLI J., 2017, vol. 16, pp. 340–353.Google Scholar
- 39.Pechanova, O., Zicha, J., Paulis, L., et al., The effect of N-acetyl cysteine and melatonin in adult spontaneously hypertensive rats with established hypertension, Eur. J. Pharmacol., 2007, vol. 561, nos. 1–3, pp. 129–136.Google Scholar
- 43.Romerowicz-Misielak, M., Oren, D.A., Sowa-Kucma, M., et al., Changes in melatonin synthesis parameters after carbon monoxide concentration increase in the cavernous sinus, J. Physiol. Pharmacol., 2015, vol. 66, no. 4, pp. 505–514.Google Scholar
- 46.Sánchez-Hidalgo, M., Guerrero Montavez, J.M., Carrascosa-Salmoral Mdel, P., et al., Decreased MT1 and MT2 melatonin receptor expression in extrapineal tissues of the rat during physiological aging, J. Pineal Res., 2009, vol. 46, no. 1, pp. 29–35.Google Scholar