Vasorelaxant effects of cardamonin and alpinetin from Alpinia henryi K. Schum.

The vascular effects of cardamonin and alpinetin from Alpinia henryi K. Sch um. were examined in the rat isolated mesenteric arteries. H-1 and C-13 nuc lear magnetic resonance spectra showed that cardamonin is present in trans- form, and single-crystal radiographic structure revealed that alpinetin is present in S configuration. Both cardamonin and alpinetin produced a rightw ard shift in the concentration-response curve for phenylephrine in a noncom petitive manner, and they induced relaxation of phenylephrine-preconstricte d arteries with respective mean inhibitory concentrations (IC50) of 9.3 +/- 0.6 muM and 17.5 +/- 2.8 muM. Both compounds also relaxed arteries precons tricted by endothelin I or U46619, Their relaxant effects were decreased in endothelium-removed rings. Pretreatment with N-G-nitro-L-arginine methyl e ster or methylene blue inhibited relaxation induced by both agents, and pre treatment with L-arginine reversed the effect of N-G-nitro-L-arginine methy l ester on cardamonin-induced endothelium-dependent relaxation. The relaxan t effects of cardamonin and alpinetin were unaffected by indomethacin (3 mu M). Cardamonin and alpinetin inhibited 60 mM K+-induced contraction with re spective IC50 of 11.5 +/- 0.3 muM and 37.9 +/- 3.6 muM. In addition, both a gents inhibited the transient contraction induced by 3 muM phenylephrine or by 10 mM caffeine in Ca2+-free Krebs solution, Finally, these two agents a lso concentration dependently relax the arteries preconstricted by 1 muM ph orbol 12,13-diacetate in Ca2+-free Krebs solution. These results indicate t hat purified cardamonin and alpinetin from A. henryi K, Schum, relaxed rat mesenteric arteries through multiple mechanisms. They induced both endothel ium-dependent and -independent relaxation; the former is likely mediated by nitric oxide whereas the latter is probably mediated through nonselective inhibition of Ca2+ influx and intracellular Ca2+ release and inhibition of the protein kinase C-dependent contractile mechanism.