Mechanism of vasorelaxation of thoracic aorta caused by xanthone.
The effect of xanthone on smooth muscle was studied in thoracic aorta isolated from rats. Xanthone relaxed the norepinephrine-induced contraction of rat thoracic aorta. This relaxing effect of xanthone persisted in endothelium-denuded aorta suggesting that the relaxation induced by xanthone is endothelium-independent. The norepinephrine and high-K+-induced vasoconstriction was inhibited dose dependently in aorta pretreated with xanthone with IC50 values of 60.26 +/- 8.43 and 82.9 +/- 13.21 microM, respectively. The inositol 1,4,5-trisphosphate formation induced by norepinephrine (3 microM) in rat aorta was not affected by xanthone (10-100 microM), suggesting that the vasorelaxant effect of xanthone was not exerted on the receptor. Xanthone concentration dependently inhibited the 45Ca2+ influx induced by either norepinephrine or high-K+, suggesting that xanthone might act as a blocker of both receptor-operated and voltage-dependent Ca2+ channels. Furthermore, xanthone caused an increase in the level of intracellular cyclic adenosine 3',5'-monophosphate (cAMP), but not cyclic guanosine 3',5'-monophosphate (cGMP) content. These data suggested that the mechanism of xanthone-induced vasorelaxation might involve the increase of intracellular cyclic adenosine 3',5'-monophosphate (cAMP) content and block of Ca2+ channels.
Cheng
Y W
YW
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei.
Kang
J J
JJ
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014966:Xanthenes / Q000494:pharmacology*; D044004:Xanthones
D007295:Inositol Phosphates; D014665:Vasodilator Agents; D014966:Xanthenes; D044004:Xanthones; C009689:xanthone; D000242:Cyclic AMP; D002118:Calcium