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Mechanism of vasorelaxant effect of the indole alkaloid 12-hydroxynorfluorocurarine hydrochloride on aortic smooth muscle contraction

Ibragimov Eldor Bakhtiyor UgliCorresponding Author Ibragimov Eldor Bakhtiyor Ugli, Cell Biophysics Laboratory, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, UzbekistanZhumaev Inoyat ZulfiqorovichCell Biophysics Laboratory, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, UzbekistanZaripov Absalim AbdikarimovichDepartment of Physiology and Pathology, No.2 Tashkent State Medical University, Tashkent, UzbekistanUsmanov Pulat BekmuratovichCell Biophysics Laboratory, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, UzbekistanRustamov Shavkat YusubovichDepartment of Medical and Biological Chemistry, No.1 Tashkent State Medical University, Tashkent, UzbekistanEsimbetov Adilbay TlepovichCell Biophysics Laboratory, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, UzbekistanAdizov Shahobiddin MukhammadovichLaboratory of High Molecular Plant Substances Chemistry and Laboratory of Physical Research Methods, Institute of the Chemistry of Plant Substances, Uzbek Academy of Sciences, Tashkent, UzbekistanKurbanov Abduburkhan KuzibayevichDepartment of Histology and Medical Biology, No.1 Tashkent State Medical University, Tashkent, Uzbekistan

2026en

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Annotatsiya

This article examines the mechanism of action of 12-hydroxynorfluorocurarine hydrochloride on vascular contractile activity. The studies were conducted in vitro using rat aortic rings. The isometric force of the contractile force of the rings was measured using an FT-03 force transducer (Grass Instrument, USA). 12-Hydroxynorfluorocurarine hydrochloride produced a dose-dependent vasorelaxant response on phenylephrine-induced aortic ring contractility, with the vasorelaxant response being reduced in the absence of endothelium. The vasorelaxant effect of 12-hydroxynorfluorocurarine hydrochloride is driven by modulation of the endothelial NO synthase (eNOS), guanylate cyclase (sGC), inward-rectifier K+ channels (Kir), and Ca2+-activated K+ channels. Furthermore, when 50 mM KCl is present, this indole alkaloid was observed to diminish the force of aortic contraction induced by elevated Ca²? ion concentration. 12-Hydroxynorfluorocurarine hydrochloride has been shown to exert potent vasorelaxant effects on rat aortic preparations through both endothelium-dependent and endothelium-independent pathways. It has been shown that the vasorelaxant action of 12- hydroxynorfluorocurarine hydrochloride is mediated by blocking L-type Ca2+ channels via the eNOS/NO/sGC signalling cascade and by activating Kir channels.

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DOI: 10.7324/japs.2026.272383

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