Vasorelaxing Activity of Stilbenoid and Phenanthrene Derivatives from Brasiliorchis porphyrostele: Involvement of Smooth Muscle CaV1.2 Channels.

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 α₁ 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.