VASORELAXATION OF RAT THORACIC AORTA CAUSED BY 14-DEOXYANDROGRAPHOLIDE

1. The pharmacological effects of 14-deoxyandrographolide on rat isolated thoracic aorta were examined. 2. 14-Deoxyandrographolide (2.5-120 μmiol/L) inhibited contractions induced by phenylephrine (PE; 0.1 μmol/L) and high K⁺ (80mmol/L) in a concentration-dependent manner in endothelium-intact aorta. The effect was attenuated in endo-thelium-denuded aorta without modifying the maximal response. Like verapamil, 14-deoxyandrographolide produced a much greater vasorelaxant effect in aorta precontracted by KCI than by PE. 14-Deoxyandrographolide (20-60 μmol/L) also inhibited responses of the rat aorta to PE. 3. In Ca²⁺-free medium (KCI 55mmol/L), 14-deoxyandrographolide (20-80 μmol/L) antagonized Ca²⁺-induced vasocon-traction in a concentration-dependent manner and transient contractions induced by both caffeine (10mmol/L) and noradrenaline (1μmol/L) were suppressed or almost abolished by 14-deoxyandrographolide. 4. The vasorelaxant effect of 14-deoxyandrographolide was partially antagonized by N^G-nitro-L -arginine methyl ester (25 μmol/L), a specific and competitive nitric oxide synthase (NOS) inhibitor, and methylene blue (10 μmol/L), a soluble guanylate cyclase inhibitor, but was not affected by indomethacin (20 μmol/L), a cyclo-oxygenase inhibitor, or glibenclamide (10 μmol/L), an ATP-sensitive K⁺-channel blocker. 5. These results suggest that the vasorelaxant activity of 14-deoxyandrographolide may be mediated via the activation of NOS and guanylate cyclase, as well as the blockade of Ca²⁺ influx through both voltage- and receptor-operated Ca²⁺ channels.