Zaporizhzhia State Medical and Pharmaceutical University, Zaporizhzhia, Ukraine
DOI 10.32782/2226-2008-2025-4-1
Given the high prevalence of arterial hypertension in the world and in our country in particular, as well as the tendency to increase in the number of younger patients, it becomes important to examine in greater depth the characteristic alterations in organs and tissues that occur under prolonged blood pressure elevation and pathogenetic treatment.
The aim of the study is to examine the characteristic changes in neuronal parameters related to energy metabolism in animals with spontaneous arterial hypertension and in correction with beta-blockers of different generations.
Materials and methods. The study involved 40 male rats with spontaneous arterial hypertension (SHR) and 10 normotensive control normotensive Wistar-Kyoto rats (WKR). The animals were divided into 5 experimental groups of 10 rats each. Different groups of experimental animals with spontaneous arterial hypertension were administered propranolol, carvedilol, and hypertril in therapeutic doses (groups 3, 4 and 5). In the experimental study, massometric, biochemical and statistical methods were used. The levels of ATP, malate, COX, and mitochondrial enzymes in animal brain homogenates were studied biochemically.
Results. In groups of rats that received beta-blockers with different properties (groups 3, 4 and 5), blood pressure was quickly stabilized to target values. Propranolol has showed a negative effect on both the content of ATP and malate as compared to the SHR results. Carvedilol has not changed the total pool of macroergic compounds ATP and malate concentrations, leaving the values at the levels of hypertensive rats. Both beta-blockers have shown no significant differences in the reduced activity of COX, mt-AsT and mt-CK. The hypertril administration has helped to completely restore the ATP and malate production, mt-AsT and mt-CK activity to normative values along with partially restored COX, in particular, the activity of mt-AsT and mt-CK enzymes was increased as compared to the SHR values.
Keywords: arterial hypertension, energy metabolism, beta-blockers, hippocampus, SHR.
REFERENCES
- Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023;41(12):1874–2071. doi: 10.1097/HJH.0000000000003480.
- NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021;398(10304):957–980. doi: 10.1016/S0140-6736(21)01330-1.
- Webb AJ, Werring DJ. New Insights Into Cerebrovascular Pathophysiology and Hypertension. Stroke. 2022;53(4):1054–1064. doi: 10.1161/STROKEAHA.121.035850.
- Maruhashi T, Higashi Y. Current topic of vascular function in hypertension in 2023-2024. Hypertens Res. 2024;47(12):3310–3317. doi: 10.1038/s41440-024-01885-3.
- Hainsworth AH, Markus HS, Schneider JA. Cerebral Small Vessel Disease, Hypertension, and Vascular Contributions to Cognitive Impairment and Dementia. Hypertension. 2024;81(1):75–86. doi: 10.1161/HYPERTENSIONAHA.123.19943.
- Baranovicova E, Kalenska D, Kaplan P, Kovalska M, Tatarkova Z, Lehotsky J. Blood and Brain Metabolites after Cerebral Ischemia. Int J Mol Sci. 2023;24(24):17302. doi: 10.3390/ijms242417302.
- Bon E, Maksimovich N, Dremza I, Gaiko D. Energy Exchange of Neurons of the Central Nervous System. Theranostics of brain, spine and neural disorders. 2023;4(4):555642. doi: 10.19080/TBSND.2022.04.555642
- Neves D, Salazar IL, Almeida RD, Silva RM. Molecular mechanisms of ischemia and glutamate excitotoxicity. Life Sci. 2023;328:121814. doi: 10.1016/j.lfs.2023.121814.
- Verma M, Lizama BN, Chu CT. Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration. Transl Neurodegener. 2022;11(1):3. doi: 10.1186/s40035-021-00278-7.
- Mahfoud F, Wang J, Ray S. The current position of β-blockers in hypertension: guidelines and clinical practice. Curr Med Res Opin. 2024;40(sup1):25–32. doi: 10.1080/03007995.2024.2318003.
- Kulaiets NM, Kulaiets VM. Association of β1-and β2-adrenergic receptor gene polymorphisms with the effectiveness of bisoprolol and carvedilol in patients with heart failure of ischemic etiology. Ukrainskyi Zhurnal Sertsevo Sudynnoi Khirurhii. 2024;32(3):28–37. (in Ukrainian). doi: https://doi.org/10.30702/ujcvs/24.32(03)/KK048-2837.
- Fragasso G, Margonato A, Spoladore R, Lopaschuk GD. Metabolic effects of cardiovascular drugs. Trends Cardiovasc Med. 2019;29(3):176–187. doi: 10.1016/j.tcm.2018.08.001.
- Belenichev I, Bukhtiyarova N, Ryzhenko V, et al. Methodological Approaches to Experimental Evaluation of Neuroprotective Action of Potential Drugs. Int J Mol Sci. 2024;25(19):10475. doi: 10.3390/ijms251910475.
- Villa, Roberto Federico et al. “Effects of Chronic Hypertension on the Energy Metabolism of Cerebral Cortex Mitochondria in Normotensive and in Spontaneously Hypertensive Rats During Aging”. Neuromolecular medicine. Vol. 26,1 2. 23 Feb. 2024, doi: 10.1007/s12017-023-08772-z.
- Belenichev I, Popazova O, Bukhtiyarova N, et al. Targeting Mitochondrial Dysfunction in Cerebral Ischemia: Advances in Pharmacological Interventions. Antioxidants (Basel). 2025;14(1):108. doi: 10.3390/antiox14010108.
- Flores-Romero, Hector et al. “Mitochondrial pores at the crossroad between cell death and inflammatory signaling.” Molecular cell vol. 2023; 83(6): 843–856. doi: 10.1016/j.molcel.2023.02.021.
- Mazur I, Belenichev I, Kucherenko L, et al. Antihypertensive and cardioprotective effects of new compound 1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide (Hypertril). Eur J Pharmacol. 2019;853:336–344. doi: 10.1016/j.ejphar.2019.04.013.
- Belenichev I, Goncharov O, Bukhtiyarova N, et al. Beta-Blockers of Different Generations: Features of Influence on the Disturbances of Myocardial Energy Metabolism in Doxorubicin-Induced Chronic Heart Failure in Rats. Biomedicines. 2024;12(9):1957. doi: 10.3390/biomedicines12091957.
