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

The vascular effects of cardamonin and alpinetin from Alpinia henryi K. Schum. were examined in the rat isolated mesenteric arteries. 1H and 13C nuclear 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 rightward shift in the concentration-response curve for phenylephrine in a noncompetitive manner, and they induced relaxation of phenylephrine-preconstricted arteries with respective mean inhibitory concentrations (IC50) of 9.3+/-0.6 microM and 27.5+/-2.8 microM. Both compounds also relaxed arteries preconstricted by endothelin I or U46619. Their relaxant effects were decreased in endothelium-removed rings. Pretreatment with N(G)-nitro-L-arginine methyl ester or methylene blue inhibited relaxation induced by both agents, and pretreatment with L-arginine reversed the effect of N(G)-nitro-L-arginine methyl ester on cardamonin-induced endothelium-dependent relaxation. The relaxant effects of cardamonin and alpinetin were unaffected by indomethacin (3 microM). Cardamonin and alpinetin inhibited 60 mM K+-induced contraction with respective IC50 of 11.5+/-0.3 microM and 37.9+/-3.6 microM. In addition, both agents inhibited the transient contraction induced by 3 microM phenylephrine or by 10 mM caffeine in Ca2+-free Krebs solution. Finally, these two agents also concentration dependently relax the arteries preconstricted by 1 microM phorbol 12,13-diacetate in Ca2+-free Krebs solution. These results indicate that purified cardamonin and alpinetin from A. henryi K. Schum. relaxed rat mesenteric arteries through multiple mechanisms. They induced both endothelium-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.