Antihypertensive Effects of a Soluble Guanylate Cyclase Stimulator

• Published in: Bulletin of experimental biology and medicine 2022-11, Vol.174 (1), p.33-36
• Main Authors: Bykov, V. V., Birulina, Yu. G., Nosarev, A. V., Vengerovskii, A. I., Udut, V. V.
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antihypertensive Agents - pharmacology; Antihypertensives; Aorta; Biomedical and Life Sciences; Biomedicine; Blood Pressure - drug effects; Cell Biology; Coronary vessels; Dosage and administration; Drug dosages; Endothelium; Guanylate cyclase; Hypertension; Internal Medicine; Isosorbide dinitrate; Laboratory Medicine; Muscle contraction; Nitric oxide; Oral administration; Oxindoles - pharmacology; Pathology; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Smooth muscle; Soluble Guanylyl Cyclase - metabolism; Vasodilation; Vasodilator Agents - pharmacology; Vasodilators
• ISSN: 0007-4888; 1573-8221
• DOI: 10.1007/s10517-022-05643-8

We studied antihypertensive activity of an indolinone derivative (compound GRS), a soluble guanylate cyclase stimulator and a drug with previously proven antiaggregant effects. Contraction activity of isolated aorta segments of Wistar-Kyoto (WKY) rats was assessed in vitro using a mechanographic method. Addition of GRS (0.1-100 μМ) resulted in dose-dependent relaxation of endothelium-denuded aorta segments. Pretreatment of aorta smooth muscle segments with a specific inhibitor of soluble guanylate cyclase (ODQ, 1 μM) weakened the vasodilatory effect of GRS. Antihypertensive activity of the indolinone derivative GRS was studied in spontaneously hypertensive SHR rats. Single oral administration of 5 and 10 mg/kg GRS was followed by a significant dose-dependent reduction of systolic and diastolic BP in SHR rats. Antihypertensive effect of GRS in a dose of 5 mg/kg was more potent than that of the reference drug isosorbide dinitrate. GRS in a dose of 10 mg/kg did not affect systolic and diastolic BP in normotensive WKY rats.