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 EC(50) 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 BaCl(2) 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(2alpha), 5-HT, dopamine, vasopressin, endothelin-1 and PE .The paeonol incubation also significantly attenuated KCl-induced contraction which mainly depended on Ca(2+) influx. In Ca(2+)-free medium (containing 10(-4)M of EGTA and 60mM of KCl), paeonol suppressed the contraction curve of CaCl(2) . In addition, paeonol also inhibited contraction by PE in Ca(2+) free solution (containing 10(-4)M of EGTA) which mainly relied on intracellular Ca(2+) release. Whole patch 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 Ca(2+) channel, as well as intracellular Ca(2+) release were all inhibited by paeonol. An intracellular Ca(2+) regulatory mechanism may be responsible to potent vasodilatory effect of paeonol. Copyright © 2010. Published by Elsevier Inc.

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Tags: Dopaminergic Medicine

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