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Current Topics in Pharmacology   Volumes    Volume 22 
Efficiency of the application of the 1.3-oxazole-4-il-phosphonic acid derivative on the sustained arterial hypertension model in rats
I. Nizhenkovska, K. Sedko, O. I. Golovchenko, O. V. Golovchenko
Pages: 63 - 68
Number of pages: 6
Current Topics in Pharmacology
Volume 22 

Copyright © 2018 Research Trends. All rights reserved

The actual direction of modern pharmacology lies in the search for new biologically active compounds with antihypertensive action for the further development of original drugs. The 1.3-oxazole-4-il-phosphonic acid derivative is a new original compound, which, according to the previous experimental studies in vitro, has vasodilatory activity and is promising for further study as an antihypertensive agent. The purpose of the paper is to study the effectiveness of the 1.3-oxazole-4-il-phosphonic acid derivative for the prophylaxis and treatment of arterial hypertension, modeled in unanesthetized rats. The studies were carried out in white Wistar rats. Sustained arterial hypertension was modeled by salt loading with free access to a salt drink of 1% sodium chloride solution for 21 days. Mean arterial pressure (MAP) and heart rate in unanesthetized rats were recorded using a sphygmomanometric method with the help of a specialized cuff with a heart rate sensor mounted on the rat’s tail and a frequency analysis of blood flow oscillations. On intraperitoneal administration of the 1.3-oxazole-4-il-phosphonic acid derivative at the dose of 25 mg/kg for 7 days in normotensive unanesthetized rats, the mean arterial pressure remained practically unchanged, with the heart rate rising by 12.0% on the 7th day (P < 0.05), which could be due to the inclusion of compensatory mechanisms for the cardiovascular system regulation. In the treatment regimen of single intraperitoneal administration of 25 mg/kg oxazole derivative to the rats with saline-induced arterial hypertension for 7 days, the studied compound showed a pronounced hypotensive effect. The latent period of the test substance is 30-40 minutes. On the first day after administration of the oxazole derivative, the mean arterial pressure decreased by 27.0% (P < 0.05), and on the 7th day by 19.4% (P < 0.05) relative to the data recorded in animals with arterial hypertension. The hypotensive effect of the oxazole derivative is comparable to the effect of amlodipine, the test compound being non-toxic unlike amlodipine, since the LD50 of the oxazole derivative is 5 times higher than amlodipine. In conditions of salt load, the test compound prevents the formation of arterial hypertension. 7-day administration of the oxazole derivative against a background of elevated mean arterial pressure shows a hypotensive effect and normalizes heart rate.
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