Vascular dilation by paeonol — A mechanism study

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• 作者：Ya-juan Li ; Jun-Xiang Bao ; Jin-wen Xu ; Ferid Murad ; Ka Bian
• 关键词：Paeonol ; Vasodilation ; Endothelium ; Vascular smooth muscle cell ; Ca²⁺ channel
• 刊名：Vascular Pharmacology
• 出版年：2010
• 出版时间：September-October 2010
• 年：2010
• 卷：53
• 期：3-4
• 页码：169-176
• 全文大小：1340 K

文摘

The goal of this study was to investigate the mechanism underlaying the vasodilatory effect of paeonol, a major active element from the root bark of Chinese herbs Paeonia suffruticosa Andr. and Cynanchum paniculatum (Bunge) Kitagawa. Paeonol relaxed isolated rat aorta rings by 95.6 % while the 10⁻⁶ M forskolin-induced vasodilatation used as 100 % . The EC₅₀ of vasodilatation by paeonol is 2.9 × 10⁻⁴ M. Although paeonol exerted endothelium-independent relaxation, L-NAME treatment inhibited paeonol-induced vasodilation of endothelium intact rings, while indomethacin did not. Both L-NAME and ODQ did not affect paeonol relaxation in the rings without endothelium. In addition, paeonol markedly elevated NO generation in cultured endothelial cells. Pre-treatment of propranolol, glibenclamide, TEA and BaCl₂ did not affect paeonol relaxation of endothelium removed rings. On the other hand, pre-treated of rings (without endothelium) with paeonol markedly blocked vasoconstriction induced by AngII, PGF_2α, 5-HT, dopamine, vasopressin, endothelin-1 and PE. The paeonol incubation also significantly attenuated KCl-induced contraction which mainly depended on Ca²⁺ influx. In Ca²⁺-free medium (containing 10⁻⁴ M of EGTA and 60 mM of KCl), paeonol suppressed the contraction curve of CaCl₂. In addition, paeonol also inhibited contraction by PE in Ca²⁺ free solution (containing 10⁻⁴ M of EGTA) which mainly relied on intracellular Ca²⁺ release. Whole-cell patch-clamp experiment showed that paeonol shifted the I–V curve and the peak value of calcium currents was significantly inhibited. In conclusion, our study suggested that voltage-dependent and receptor-operated Ca²⁺ channel, as well as intracellular Ca²⁺ release were all inhibited by paeonol. An intracellular Ca²⁺ regulatory mechanism may be responsible to potent vasodilatory effect of paeonol.