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Pharmacological Effects of a New Soluble Guanylate Cyclase Stimulator in Experimental Ischemic Stroke

  • GENERAL PATHOLOGY AND PATHOLOGICAL PHYSIOLOGY
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We studied the action of a new indolinone derivative GRS, acetylsalicylic acid (ASA), and their combination on platelet aggregation, vasodilatory endothelial function, neurological status, and cerebral infarction area in experimental focal cerebral ischemia/reperfusion in rats. GRS compound (10 mg/kg), ASA (10 mg/kg), and their combination in the same doses were administered orally once a day as a suspension in 1% starch solution over 5 days after pathology modeling. Sham-operated and control animals were administered 1% starch solution. On day 5 after pathology modeling, platelet aggregation and brain damage area were studied in a half of rats in each group, and the vasodilatory function of the endothelium was studied in the other half. Neurological deficit was assessed 4 h and 1, 3, and 5 days after pathology modeling. GRS compound and ASA equally effectively prevent platelet aggregation and the development of neurological deficit in rats. GRS compound restores the vasodilatory effects of the endothelium, but only ASA contributes to reduction of the cerebral infarction area. In case of combined administration, GRS and ASA do not exhibit synergy in their antiaggregant effect.

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References

  1. Hofmann F, Feil R, Kleppisch T, Schlossmann J. Function of cGMP-dependent protein kinases as revealed by gene deletion. Physiol. Rev. 2006;86(1):1-23. https://doi.org/10.1152/physrev.00015.2005

    Article  CAS  PubMed  Google Scholar 

  2. Makhoul S, Walter E, Pagel O, Walter U, Sickmann A, Gambaryan S, Smolenski A, Zahedi RP, Jurk K. Effects of the NO/soluble guanylate cyclase/cGMP system on the functions of human platelets. Nitric Oxide. 2018;76:71-80. https://doi.org/10.1016/j.niox.2018.03.008

    Article  CAS  PubMed  Google Scholar 

  3. Sandner P, Zimmer DP, Milne GT, Follmann M, Hobbs A, Stasch JP. Soluble guanylate cyclase stimulators and activators. Handb. Exp. Pharmacol. 2021;264:355-394. https://doi.org/10.1007/164_2018_197

    Article  CAS  PubMed  Google Scholar 

  4. Ischemic Stroke and Transient Ischemic Attack in Adults: Clinical Recommendations.URL: https://cr.minzdrav.gov.ru/schema/171_2

  5. Bykov VV, Chernysheva GA, Smolyakova VI, Serebrov VYu, Khazanov VA, Udut VV. Antiplatelet activity of a new indolinone derivative. Eksper. Klin. Farmakol. 2019;82(7):10-13. Russian. https://doi.org/10.30906/0869-2092-2019-82-7-10-13

  6. Hamilos M, Petousis S, Parthenakis F. Interaction between platelets and endothelium: from pathophysiology to new therapeutic options. Cardiovasc. Diagn. Ther. 2018;8(5):568-580. https://doi.org/10.21037/cdt.2018.07.01

  7. Domashenko MA, Maksimova MYu, Tanashyan MM. Modern view on the antiplatelet drugs appointment for secondary prevention of noncardioembolic ischemic stroke. Effekt. Farmakoter. 2018;(24):82-87. Russian.

  8. Vlasov TD, Petrischev NN, Lazovskaya OA. Endothelial dysfunction. Do we understand this term properly? Vestn. Anesteziol. Reanimatol. 2020;17(2):76-84. Russian. https://doi.org/10.21292/2078-5658-2020-17-2-76-84

  9. Jiang X, Liu X, Liu X, Wu X, Jose PA, Liu M, Yang Z. Low-dose aspirin treatment attenuates male rat salt-sensitive hypertension via platelet Cyclooxygenase 1 and complement cascade pathway. J. Am. Heart Assoc. 2020;9(1):e013470. https://doi.org/10.1161/JAHA.119.013470

    Article  CAS  PubMed  Google Scholar 

  10. Zhang H, Shen Y, Wang W, Gao H. Rat model of focal cerebral ischemia in the dominant hemisphere. Int. J. Clin. Exp. Med. 2015;8(1):504-511.

    PubMed  PubMed Central  Google Scholar 

  11. Sidekhmenova AV, Aliev OI, Anishchenko AM, Shamanaev AYu, Fedorova EP, Plotnikov MB. Dynamics of indicators of platelets, white blood cells, and functional activity of the endothelium in young SHR rats. Sib. Med. Zh. (Tomsk). 2015;30(3):61-65. Russian. https://doi.org/10.29001/2073-8552-2015-30-3-61-65

  12. Mishra P, Pandey CM, Singh U, Keshri A, Sabaretnam M. Selection of appropriate statistical methods for data analysis. Ann. Card. Anaesth. 2019;22(3):297-301. https://doi.org/10.4103/aca.ACA_248_18

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bykov VV, Smol’yakova VI, Chernysheva GA, Aliev OI, Anishchenko AM, Sidekhmenova AV, Dunaeva OI, Stankevich SA, Khazanov VA. Effects of a new antithrombotic drug GRS, a soluble guanylate cyclase stimulator, on endothelial dysfunction in rats with myocardial infarction. Bull. Exp. Biol. Med. 2022;172(6):709-712. https://doi.org/10.1007/s10517-022-05461-y

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Authors and Affiliations

  1. IPHAR (Innovative Pharmacology Research, LLC), Tomsk, Russia

    V. V. Bykov, A. V. Bykova, V. S. Motov, V. V. Larchenko & V. A. Khazanov

  2. Siberian State Medical University, Ministry of Health of the Russian Federation, Tomsk, Russia

    V. V. Bykov, V. V. Larchenko & A. I. Vengerovskii

  3. E. D. Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia

    G. A. Chernysheva, V. I. Smol’yakova, O. I. Aliev & V. V. Udut

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  1. V. V. Bykov
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  2. A. V. Bykova
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  3. V. S. Motov
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  4. V. V. Larchenko
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  5. G. A. Chernysheva
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  6. V. I. Smol’yakova
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  7. O. I. Aliev
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  8. V. A. Khazanov
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  9. A. I. Vengerovskii
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  10. V. V. Udut
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Correspondence to V. V. Bykov.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 175, No. 6, pp. 701-704, June, 2023

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Bykov, V.V., Bykova, A.V., Motov, V.S. et al. Pharmacological Effects of a New Soluble Guanylate Cyclase Stimulator in Experimental Ischemic Stroke. Bull Exp Biol Med 175, 749–752 (2023). https://doi.org/10.1007/s10517-023-05938-4

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  • DOI: https://doi.org/10.1007/s10517-023-05938-4

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