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

• Published in: Bulletin of experimental biology and medicine Vol. 175; no. 6; pp. 749 - 752
• Main Authors: Bykov, V. V., Bykova, A. V., Motov, V. S., Larchenko, V. V., Chernysheva, G. A., Smol’yakova, V. I., Aliev, O. I., Khazanov, V. A., Vengerovskii, A. I., Udut, V. V.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2023; Springer; Springer Nature B.V
• Subjects: Acetylsalicylic acid; Aspirin; Biomedical and Life Sciences; Biomedicine; Blood vessels; Brain damage; Brain injury; Cell Biology; Cerebral infarction; Dilatation; Endothelium; General Pathology and Pathological Physiology; Guanylate cyclase; Internal Medicine; Ischemia; Laboratory Medicine; Oral administration; Pathology; Platelet aggregation; Reperfusion; Stroke; Stroke (Disease); Vasodilators; soluble guanylate cyclase stimulator; experimental model of ischemic stroke; endothelial dysfunction; indolinone derivative; platelet aggregation
• ISSN: 0007-4888; 1573-8221
• DOI: 10.1007/s10517-023-05938-4

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.