Vasorelaxing Activity of Stilbenoid and Phenanthrene Derivatives from Brasiliorchis porphyrostele: Involvement of Smooth Muscle Ca_V1.2 Channels

Abstract

Five compounds, 3,4′-dihydroxy-3′,5,5′-trimethoxydihydrostilbene, 1; 3,4′-ihydroxy-3′,5′-dimethoxydihydrostilbene, 2; 3,4′-dihydroxy-5,5′-dimethoxydihydrostilbene, 3; 9,10-dihydro-2,7-dihydroxy-4,6-dimethoxyphenanthrene, 4; and the previously unreported 1,2,6,7-tetrahydroxy-4-methoxyphenanthrene, 5 were isolated from the South American orchid, Brasiliorchis porphyrostele. An in-depth analysis of their vascular effects was performed on in vitro rat aorta rings and tail main artery myocytes. Compounds 1 – 4 were shown to possess vasorelaxant activity on rings pre-contracted by the α ₁ receptor agonist phenylephrine, the Ca_V1.2 stimulator (S)-(−)-Bay K 8644, or depolarized with high K⁺ concentrations. However, compound 5 was active solely on rings stimulated by 25 mM but not 60 mM K⁺. The spasmolytic activity of compounds 1 and 4 was significantly affected by the presence of an intact endothelium. The K_ATP channel blocker glibenclamide and the K_V channel blocker 4-aminopyridine significantly antagonized the vasorelaxant activity of compounds 4 and 1, respectively. In patch-clamp experiments, compounds 1 – 4 inhibited Ba²⁺ current through Ca_V1.2 channels in a concentration-dependent manner, whereas neither compound 4 nor compound 1 affected K⁺ currents through K_ATP and K_V channels, respectively. The present in vitro, comprehensive study demonstrates that Brasiliorchis porphyrostele may represent a source of vasoactive agents potentially useful for the development of novel antihypertensive agents that has now to be validated in vivo in animal models of hypertension.

Key words

Brasiliorchis porphyrostele - phenanthrenes - stilbenoids - vasorelaxing - vascular Ca_V1.2 channel - vascular endothelium - Orchidaceae

• References

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