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

Ibragimov Eldor Bakhtiyor Ugli,  Zhumaev Inoyat Zulfiqorovich,  Zaripov Abdisalim Abdikarimovich,  Usmanov Pulat Bekmuratovich,  Rustamov Shavkat Yusubovich,  Esimbetov Adilbay Tlepovich,  Adizov Shahobiddin Mukhammadovich,  Kurbanov Abduburkhan Kuzibayevich   

Ibragimov Eldor Bakhtiyor Ugli1,2, Zhumaev Inoyat Zulfiqorovich1, Zaripov Abdisalim Abdikarimovich1,3, Usmanov Pulat Bekmuratovich1, Rustamov Shavkat Yusubovich1,4, Esimbetov Adilbay Tlepovich1, Adizov Shahobiddin Mukhammadovich5, Kurbanov Abduburkhan Kuzibayevich2

1Cell Biophysics Laboratory, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, Uzbekistan.

2Department of Histology and Medical Biology, No. 1 Tashkent State Medical University, Tashkent, Uzbekistan.

3Department of Physiology and Pathology, No. 2 Tashkent State Medical University, Tashkent, Uzbekistan.

4Department of Medical and Biological Chemistry, No. 1 Tashkent State Medical University, Tashkent, Uzbekistan.

5Laboratory of High Molecular Plant Substances Chemistry and Laboratory of Physical Research Methods, Institute of the Chemistry of Plant Substances, Uzbek Academy of Sciences, Tashkent, Uzbekistan.

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Published:  Dec 18, 2025

DOI: 10.7324/JAPS.2026.272383
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Abstract

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.


Keyword:     Indole alkaloid aorta vasorelaxant endothelium ion channel

Citation:

Ibragimov EBU, Zhumaev IZ, Zaripov AA, Usmanov PB, Rustamov ShY, Esimbetov AT, Adizov ShM, Kurbanov AK. Mechanism of vasorelaxant effect of the indole alkaloid 12-hydroxynorfluorocurarine hydrochloride on aortic smooth muscle contraction. J Appl Pharm Sci. 2025. Article in Press. http://doi.org/10.7324/JAPS.2026.272383

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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