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.
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 mumol/l and 15 mumol/l (for Ca2+ concentration of 1 mmol/l), respectively. Cromakalim (0.2-10 mumol/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 15 mmol/l K(+)-induced contraction. Nifedipine (1 mumol/l), dictamine (100 mumol/l) and fraxinellone (100 mumol/l) relaxed the aortic contraction caused by KCl or Bay K 8644. The tonic contraction elicited by noradrenaline (NA, 3 mumol/l) was also relaxed by dictamine (500 mumol/l), but not by fraxinellone (500 mumol/l) in the nifedipine (1 mumol/l)-treated aorta. This relaxing effect of dictamine persisted in endothelium-denuded aorta. Glibenclamide (10 mumol/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 mumol/l) did not affect tonic contraction of NA which are reduced by H-7 (1 mumol/l) in Ca(2+)-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.
Yu
S M
SM
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Ko
F N
FN
Su
M J
MJ
Wu
T S
TS
Wang
M L
ML
Huang
T F
TF
Teng
C M
CM
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001572:Benzofurans / Q000494:pharmacology*; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D019806:Cromakalim; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011804:Quinolines; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D000470:Alkaloids; D001572:Benzofurans; D001578:Benzopyrans; D002121:Calcium Channel Blockers; D004365:Drugs, Chinese Herbal; D015221:Potassium Channels; D011758:Pyrroles; D011804:Quinolines; D019806:Cromakalim; C075391:fraxinellone; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D000242:Cyclic AMP; D006152:Cyclic GMP; C026398:dictamnine; D005905:Glyburide; D002118:Calcium; D009638:Norepinephrine