Pantan Rungusa, Onsa-Ard Amnart, Tocharus Jiraporn, Wonganan Orawan, Suksamrarn Apichart, Tocharus Chainarong
Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Department of Biochemistry, Faculty of Medical Science, Phayao University, Phayao 56000, Thailand.
Life Sci. 2014 Oct 22;116(1):31-6. doi: 10.1016/j.lfs.2014.08.010. Epub 2014 Aug 21.
The aim of this study is to investigate the vasorelaxant effect of 16-O-acetyldihydroisosteviol (ADIS) and its underlying mechanisms in isolated rat aorta.
Rat aortic rings were isolated, suspended in organ baths containing Kreb's solution, maintained at 37°C, and mounted on tungsten wire and continuously bubbled with a mixture of 95% O2 and 5% CO2 under a resting tension of 1g. The vasorelaxant effects of ADIS were investigated by means of isometric tension recording experiment.
ADIS (0.1μM-3mM) induced relaxation of aortic rings pre-contracted by phenylephrine (PE, 10μM) and KCl (80mM) with intact-endothelium (Emax=79.26±3.74 and 79.88±3.79, respectively) or denuded-endothelium (Emax=88.05±3.69 and 78.22±6.86, respectively). In depolarization Ca(2+)-free solution, ADIS inhibits calcium chloride (CaCl2)-induced contraction in endothelium-denuded rings in a concentration-dependent manner. In addition, ADIS attenuates transient contractions in Ca(2+)-free medium containing EGTA (1mM) induced by PE (10μM) and caffeine (20mM). By contrast, relaxation was not affected by tetraethylammonium (TEA, 5mM), 4-aminopyridine (4-AP, 1mM), glibenclamide (10μM), barium chloride (BaCl2, 1mM), and 1H-[1,2,3]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ, 1μM).
These findings reveal the vasorelaxant effect of ADIS, through endothelium-independent pathway. It acts as a Ca(2+) channel blocker through both intracellular and extracellular Ca(2+) release.
本研究旨在探讨16 - O - 乙酰基二氢异甜菊醇（ADIS）对离体大鼠主动脉的血管舒张作用及其潜在机制。
分离大鼠主动脉环，悬挂于含Krebs溶液的器官浴槽中，维持在37°C，固定在钨丝上，并在1g静息张力下用95% O₂和5% CO₂的混合气体持续鼓泡。通过等长张力记录实验研究ADIS的血管舒张作用。
ADIS（0.1μM - 3mM）可使由去氧肾上腺素（PE，10μM）和氯化钾（80mM）预收缩的完整内皮（Emax分别为79.26±3.74和79.88±3.79）或去内皮（Emax分别为88.05±3.69和78.22±6.86）的主动脉环舒张。在去极化无钙溶液中，ADIS以浓度依赖方式抑制氯化钙（CaCl₂）诱导的去内皮环收缩。此外，ADIS可减弱由PE（10μM）和咖啡因（20mM）在含乙二醇双四乙酸（EGTA，1mM）的无钙培养基中诱导的瞬时收缩。相比之下，去甲肾上腺素（TEA，5mM）、4 - 氨基吡啶（4 - AP，1mM）、格列本脲（10μM）、氯化钡（BaCl₂，1mM）和1H - [1,2,3]恶二唑并[4,3 - α]喹喔啉 - 1 - 酮（ODQ，1μM）对舒张无影响。
这些发现揭示了ADIS通过非内皮依赖途径产生的血管舒张作用。它通过细胞内和细胞外钙释放作为一种钙通道阻滞剂发挥作用。
