Correction of rats’ systemic and cerebral blood circulation with the cerebral ischemia-reperfusion model using new neuropeptides, ACTH15-18 derivatives

R. D. Deiko, S. Yu. Shtrygol, O. O. Kolobov, O. A. Khodakivskiy, L. B. Ivantsyk

Abstract


Cerebrovascular diseases are leading problems of the modern medicine and pharmacy. That is why creation of new neuroprotectors and their introduction into clinical practice is a topical issue. A series of oligopeptides, 15-18 adrenocorticotropic hormone link derivatives has been created. These neuropeptides are compounds with the general formula of Acetyl-Lys-Lys-Arg-Arg-amide. They are nontoxic compounds and resistant to action of blood aminopeptidases. Their composition includes unnatural D-aminoacids and their N-methylated forms. The previous studies have determined their anti-ischemic and nootropic action, and a favourable spectrum of psychotropic properties. The question about mechanisms of the anti-hypoxic action of compound Acetyl-(D-Lys)-Lys-Arg-Arg-amide (KK-1) remains open. The aim of our investigation is to study effect of neuropeptide KK-1 on the hemodynamic parameters, as well as blood oxygenation against the background of ischemia-reperfusion in the rats’ brain. The volume speed of the blood flow in the internal carotid artery, blood pressure in the femoral artery, the central venous pressure and blood oxygenation were measured. The ability of peptide KK-1 to restore the initial level of blood pressure in the femoral artery and central venous pressure within 7 days has been found. The volume speed of the blood flow in the internal carotid artery was sufficient for brain blood supply during all post-ischemic period. The level of blood oxygenation varied from 97% to 98%, tending to the norm. By the effect on the indicators listed neuropeptide KK-1 exceeds the action of the reference drug citicoline. The positive effect of peptide KK-1 on the performance of the system and cerebral blood flow and blood oxygen saturation against the background of cerebral ischemia confirms its anti-ischemic and cerebroprotective effect. The pharmacological drug is promising for further experimental and clinical studies.


Keywords


experiment; cerebral blood circulation; systemic blood circulation; ischemia-reperfusion; neuropeptides

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DOI: https://doi.org/10.24959/cphj.15.1348

Abbreviated key title: Klìn. farm.

ISSN 2518-1572 (Online), ISSN 1562-725X (Print)