Vasorelaxing effect in rat thoracic aorta caused by fraxinellone and dictamine isolated from the Chinese herb Dictamnus dasycarpus Turcz: comparison with cromakalim and Ca2+ channel blockers

Summary The components of Dictamnus dasycarpus Turcz were tested for their vasorelaxing effect on the rat aorta, and fraxinellone and dictamine were shown to be effective vasorelaxants. In high K⁺ (60 mmol/l) medium, Ca²⁺ (0.03 to 3 mmol/l)-induced vasoconstriction was inhibited concentration-dependently by both agents. The IC₅₀ for fraxinellone and dictamine were calculated to be about 25 mol/l and 15 mol/l (for Ca²⁺) concentration of (1 mmol/l), respectively. Cromakalim (0.2–10) mol/l relaxed aortic rings precontracted with 15 but not 60 mmol/l of K⁺. Fraxinellone and verapamil were more potent and effective in producing relaxation in 60 mmol/l than in 15 mmol/l K⁺-induced contraction. However, dictamine was more potent in producing relaxation in 5 mmol/l K⁺-induced contraction. Nifedipine (1 mol/l), dictamine (100 mol/l) and fraxinellone (100 mol/l) relaxed the aortic contraction caused by KCl or Bay K 8644. The tonic contraction elicited by nor adrenaline (NA, 3 mol/l) was also relaxed by dictamine (500 mol/l), but not by fraxinellone (500 mol/l) in the nifedipine (1 mol/l)-treated aorta. This relaxing effect of dictamine persisted in endothelium-denuded aorta. Glibenclamide (10 mol/l) shifted the concentration-relaxation curve of cromakalim, but not that of dictamine, to the right in rat aortic rings precontracted with NA. Dictamine (500 mol/l) did not affect tonic contraction of NA which are reduced by H-7 (1 mol/l) in Ca²⁺ depleted medium. In conclusion, fraxinellone is a selective blocker of voltage-dependent Ca²⁺ channel, while dictamine relaxed the rat aorta by suppressing the Ca²⁺ influx through both voltage-dependent and receptor-operated Ca²⁺ channels.This work was supported by a research grant from the Nationat Science Council of the Republic of China (NSC80-0420-B002-18) Send offprint requests to C. M. Teng, Pharmacological Institute, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Sect. 1, Taipei, 10018, Taiwan