VASORELAXATION OF RAT THORACIC AORTA CAUSED BY 14-DEOXYANDROGRAPHOLIDE

1. The pharmacological effects of 14-deoxyandrographolide on rat isola ted thoracic aorta were examined. 2. 14-Deoxyandrographolide (2.5-120 mu mol/L) inhibited contractions induced by phenylephrine (PE; 0.1 mu mol/L) and high K+ (80mmol/L) in a concentration-dependent manner in e ndothelium-intact aorta. The effect was attenuated in endothelium-denu ded aorta without modifying the maximal response. Like verapamil, 14-d eoxyandrographolide produced a much greater vasorelaxant effect in aor ta precontracted by KCI than by PE, 14-Deoxyandrographolide (20-60 mu mol/L) also inhibited responses of the rat aorta to PE, 3. In Ca2+-fre e medium (KCl 55 mmol/L), 14-deoxyandrographolide (20-80 mu mol/L) ant agonized Ca2+-induced vasocontraction in a concentration-dependent man ner and transient contractions induced by both caffeine (10 mmol/L) an d noradrenaline (1 mu mol/L) were suppressed or almost abolished by 14 -deoxyandrographolide. 4. The vasorelaxant effect of 14-deoxyandrograp holide was partially antagonized by N-G-nitro-L-arginine methyl ester (25 mu mol/L), a specific and competitive nitric oxide synthase (NOS) inhibitor, and methylene blue (10 mu mol/L), a soluble guanylate cycla se inhibitor, but was not affected by indomethacin (20 mu mol/L), a cy clo-oxygenase inhibitor, or glibenclamide (10 mu mol/L), an ATP-sensit ive 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.