Vasorelaxing effect in rat thoracic aorta caused by denudatin B, isolated from the Chinese herb, magnolia fargesii.
Denudatin B is an antiplatelet agent isolated from the flower buds of Magnolia fargesii. We studied the effects of denudatin B on the vasoconstriction of rat thoracic aorta induced by high potassium (K+) solution, norepinephrine (NE) and caffeine, and to elucidate its mode of action. The contraction of rat aorta caused by high K+ (60 mM) and cumulative concentrations of CaCl2 (0.03-3 mM) was inhibited concentration dependently by denudatin B with an IC50 of 21.2 micrograms/ml. NE (3 microM)-induced phasic and tonic contractions of rat aorta were inhibited by pretreatment with denudatin B (10-100 micrograms/ml). The relaxing action of denudatin B persisted in denuded aorta, in Ca2(+)-free and EGTA (2 mM)-containing medium. The vasorelaxing effects were not affected by indomethacin (20 microM), hemoglobin (10 microM) or methylene blue (50 microM) and were not accompanied by PGI2 formation. In quin-2/AM-loaded cultured rat vascular smooth muscle cells, denudatin B (100 micrograms/ml) inhibited the increase of intracellular calcium caused by NE (3 microM) in the presence or absence of extracellular calcium. Denudatin B did not affect the caffeine (10 mM)-induced contraction and the increase in intracellular calcium. Denudatin B (100 micrograms/ml) increased the cGMP, but not the cAMP level in intact and denuded aorta. The 45Ca2+ influx induced in rat aorta by high K+ (60 mM) or NE (3 microM) was markedly inhibited by denudatin B in a concentration-dependent manner. These results indicate that denudatin B relaxed vascular smooth muscle by inhibiting the Ca2+ influx through voltage-gated and receptor-operated Ca2+ channels; its effect to increase cGMP may enhance the vasorelaxation.
Yu
S M
SM
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Chen
C C
CC
Huang
Y L
YL
Tsai
C W
CW
Lin
C H
CH
Huang
T F
TF
Teng
C M
CM
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001572:Benzofurans / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis; D066298:In Vitro Techniques; D017705:Lignans; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001572:Benzofurans; D002132:Calcium Radioisotopes; D004365:Drugs, Chinese Herbal; D017705:Lignans; D002110:Caffeine; C044540:kadsurenone; D011464:Epoprostenol; D000242:Cyclic AMP; D006152:Cyclic GMP; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine