Pharmacological correction of cerebrovascular disorders in various experimental pathological conditions

Cover Page


Cite item

Full Text

Abstract

Abstract

Introduction. In the treatment of patients with cerebrovascular disorders, pharmacological correction of cerebral circulation largely depends on the character and the state of the pathological process. This determines the need to study the pharmacological regulation of the cerebral blood supply in various pathological conditions.

Objective. To study the effects of oxymethylethylpiridine succinate, nicotinoyl gamma-aminobutiric acid, nimodipine, amlodipine besylate and S-amlodipin nicotinate on the cerebral circulation of intact and ischemic rats, and to assess the effects of oxymethylethylpiridine succinate and nimodipine in experimental myocardial infarction and combined vascular pathology of the brain and heart.

Materials and methods. The cerebral circulation was evaluated using the laser Doppler flowmetry technique. Global transient ischemia was caused by occlusion of both common carotid arteries with simultaneous decrease in arterial pressure by bleeding and subsequent reinfusion. Experimental myocardial infarction was modeled by occlusion of the left coronary artery.

Results. Oxymethylethylpiridine succinate significantly increases blood supply to the brain in rats under conditions of global transient ischemia of the brain and combined vascular pathology of the brain and heart, in contrast with intact animals and animals with experimental myocardial infarction. Nicotinoyl gamma-aminobutiric acid equally increased blood circulation of the intact and the ischemic brain. Nimodipine equally increased cerebral blood flow in intact rats and in rats underwent brain ischemia, whereas this effect was significantly weakened in experimental myocardial infarction and disappeared in combined vascular pathology. S-amlodipin nicotinate and, to a lesser extent, amlodipine bisilate increased blood supply to the ischemic brain. The vasodilating effects of oxymethylethylpiridine succinate, nicotinoyl gamma-aminobutiric acid and S-amlodipin nicotinate, but not of nimodipine, were eliminated by GABAA receptor blockers.

Conclusions. The dependence of the vasodilating effect of the studied drugs on the initial state of the organism was revealed. This phenomenon should be taken into account in prescribing target pathogenetic therapy of ischemic stroke.

About the authors

Ruben S. Mirzoyan

V. V. Zakusov State Institute of Pharmacology

Author for correspondence.
Email: cerebropharm@mail.ru
Россия, Moscow

Tamara S. Gan,shina

V. V. Zakusov State Institute of Pharmacology

Email: cerebropharm@mail.ru
Россия, Moscow

Galina A. Kim

Consortium-PIK Company

Email: cerebropharm@mail.ru
Россия, Moscow

Il'ya N. Kurdyumov

V. V. Zakusov State Institute of Pharmacology

Email: cerebropharm@mail.ru
Россия, Moscow

Denis V. Maslennikov

V. V. Zakusov State Institute of Pharmacology

Email: cerebropharm@mail.ru
Россия, Moscow

Elena V. Kurza

V. V. Zakusov State Institute of Pharmacology

Email: center@test.ru
Россия, Moscow

References

  1. SuslinaZ.A.,TanashyanM.M.Antitromboticheskayaterapiyaishemicheskikhnarusheniymozgovogokrovoobrashcheniyaspozitsiydokazatel'noymeditsiny. [Antithrombotic therapy of ischemic disorders of cerebral circulation from the standpoint of evidence-based medicine]. Meditsinskoeinformatsionnoeagentstvo. 2009; 224 p. (In Russ.).
  2. Tanashian M.M., Lagoda O.V., Antonova K.V. [Chronic cerebrovascular diseases associated with metabolic syndrome: new treatment approaches]. ZhNevrolPsikhiatrIm S SKorsakova.. 2012; 11: 21-26. (In Russ.).
  3. MozaffarianD., Benjamin E.J., Go A.S., Arnett D.K et al. Executive Summary: Heart Disease and Stroke Statistics - 2016 Update: A Report from the American Heart Association. Circulation 2016; 4: 447-454.doi: 10.1161/CIR.0000000000000366 PMID: 26811276
  4. ChungY.S. et al. S-(-)-amlodipine nicotinate and process for the preparation thereof. Patent US, no. 2006/0014795 A1, 2006.
  5. Park J.Y., Kim K.A., Park P.W, et al. Comparative pharmacokinetic and pharmacodynamic characteristics of amlodipine besylate and amlodipine nicotinate in healthy subjects. Int.J.Clin.Pharmacol.Ther. 2006; 44: 641-647.doi: 10.5414/CPP44641 PMID: 17190374
  6. Kim S.A., Park S., Chung N. et al. Efficacy and safety profiles of a new S (-) -amlodipine nicotinate formulation versus racemic amlodipine besylate in adult Korean patients with mild to moderate hypertension: an 8-week, multicenter, randomized, double-blind, double-dummy, parallel-group, phase III, noninferiority clinical trial. Clin. Ther. 2008; 30(5):845-57. PMID: 18555932 doi: 10.1016/j.clinthera.2008.05.013
  7. LaiT., Zhang W.S.,WangY.T. Excitotoxicity and stroke: Identifying novel targets for neuroprotection. ProgressinNeurobiology2014; 115:157–188. PMID: 24361499 doi: 10.1016/j.pneurobio.2013.11.006
  8. Mirzoyan S.A., Kasaryan B.A., Akopyan V.P.[Decarboxylase activity of glutamic acid in the vessels of the brain]. Reports of the Academy of Sciences of the USSR in 1970; 190(5): 1241-2. (In Russ.). PMID: 5469664
  9. Mirzoyan S.A., Kasaryan B.A., Akopyan V.P.[The content and some transformations of amino acids in the tissues of the walls of the brain arteries]. Reports of the Academy of Sciences of the USSR 1974; 214 (2): 465-468. (In Russ.).
  10. Krause D.N. E. Wong, P. Degener, and E. Roberts. GABA receptors in bovine cerebral blood vessels: Binding studies with [3H] muscimol. Brain Research Bulletin 1980; 5:173-177. PMID: 6243504 doi: 10.1016/0006-8993(80)90669-1
  11. Napoleon P., Endo S., Amenta F. Autoradiographic localization of the GABAA receptor agonist [3H] muscimol in the rat cerebral vessels. Brain Research 1987; 423: 109 – 115. PMID: 2823981
  12. Mirzoyan R.S., Gan’shina T.S., Gorbunov A.A. et al. [Pharmacology of various neuromediator mechanisms of regulation of cerebral circulation]. Eksp Klin Farmakol.2014; 77(8):20-2. (In Russ.). PMID: 25335386. 2017; 80 (9): 35-39. (In Russ.).
  13. Mirzoyan R.S., Plotnikov M.B.,Gan’shina T.S. et al. [Guidelines for preclinical study of drugs for treatment of disorders of cerebral circulation and migraine. The guidelines for preclinical studies of pharmaceuticals. Part one]. Moscow: Grif K, 2012: 480-487. (InRuss.).
  14. Seropian I.M., Gonzales G.E. Experimental myocardial infarction, in Experimental surgical models in the laboratory rat. Boca Raton, 2009: 201-204.
  15. Lebedeva M.A., MedvedevaYu.S., Mirzoyan R.S. et. al. [Integral evaluation of shifts in serum homeostasis with experimental myocardial infarction]. Patol. physiol. and exper. therapy. 2013; 4: 35-40. (In Russ.).
  16. Mirzoyan R.S., Gan’shina T.S.[The new cerebrovascular preparation pikamilon]. FarmakolToksikol. 1989; 52(1): 23-6. (In Russ.). PMID: 2707413
  17. Gan’shina T. S., Kim G. A, Gnezdilova A. V. et al. [Comparative study of the effect of S-anlodipine nicotinate and amlodipine bezylate on the arterial pressure of awake rets]. EkspKlinFarmakol.2014; 77(8):20-2. (In Russ.). PMID: 25335386
  18. Kovalev G.I., Vasil’eva E.V., Salimov R.M. [The action of picamilon on prefrontal-cortex GABA receptors and behavior of C57BL/6 and BALB/C mice in closed cross-maze labyrinth]. EkspKlinFarmakol. 2017; 80 (3): 3-9. (In Russ.).

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2018 Mirzoyan R.S., Gan,shina T.S., Kim G.A., Kurdyumov I.N., Maslennikov D.V., Kurza E.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-83204 от 12.05.2022.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies