Chiou W F, Liao J F, Shum A Y, Chen C F
National Research Institute of Chinese Medicine, Taipei Hsien, Taiwan. R.O.C.
J Cardiovasc Pharmacol. 1996 Jun;27(6):845-53. doi: 10.1097/00005344-199606000-00012.
We examined the mechanisms underlying the vasorelaxant effect of dehydroevodiamine (DeHE), one of the bioactive components of the Chinese herbal drug Evodia rutaecarpa that has been shown to produce vasorelaxant and hypotension. DeHE (10(-7)-10(-4) M) concentration-dependently relaxed isolated rat mesenteric arteries precontracted with phenylephrine (PE). This vasorelaxant potency was diminished by 15% by endothelial removal, L-NG-nitro arginine, or methylene blue (MB), but not indomethacin treatment, indicating that the vasorelaxant effect of DeHE was partially endothelium dependent and mediated by nitric oxide (NO) and the cyclic GMP pathway. In endothelium-denuded preparations, DeHE caused a rightward shift of the contractile concentration-response curve (CRC) to PE in a dose-dependent manner with a pA2 value of 6.15. Maximal response was unaffected. Receptor binding assay indicated that DeHE competed with alpha 1-adrenoceptor ligand prazosin with a Ki value of 3.57 microM. Potassium channel activity-attenuating conditions such as increased level of extracellular K+ (20 mM) and treatment with the antagonist tetraethylammonium (TEA) significantly inhibited DeHE's effect, suggesting a mode of action similar to that of a potassium channel activator. In addition, high concentrations of DeHE (3 x 10(-5) and 10(-4) M) relaxed high K+ (80 mM)-evoked contraction, indicating that DeHE might possess K+ channel blocking properties. Multiple-action mechanisms, including endothelium dependence, alpha 1-adrenoceptor blockade, K+ channel activation, and Ca2+ channel blockade were probably involved in the vasorelaxant effects of DeHE.
我们研究了吴茱萸次碱（DeHE）血管舒张作用的潜在机制。吴茱萸次碱是中草药吴茱萸的生物活性成分之一，已被证明具有血管舒张和降血压作用。DeHE（10⁻⁷ - 10⁻⁴ M）能浓度依赖性地舒张预先用去氧肾上腺素（PE）预收缩的离体大鼠肠系膜动脉。去除内皮、L - NG - 硝基精氨酸或亚甲蓝（MB）可使这种血管舒张作用减弱15%，但吲哚美辛处理则无此作用，这表明DeHE的血管舒张作用部分依赖于内皮，且由一氧化氮（NO）和环鸟苷酸途径介导。在内皮剥脱的制备物中，DeHE使对PE的收缩浓度 - 反应曲线（CRC）剂量依赖性地右移，pA2值为6.15。最大反应未受影响。受体结合试验表明，DeHE与α1 - 肾上腺素能受体配体哌唑嗪竞争，Ki值为3.57 μM。钾通道活性减弱的条件，如细胞外K⁺水平升高（20 mM）和用拮抗剂四乙铵（TEA）处理，可显著抑制DeHE的作用，提示其作用方式类似于钾通道激活剂。此外，高浓度的DeHE（3×10⁻⁵和10⁻⁴ M）可舒张高K⁺（80 mM）诱发的收缩，表明DeHE可能具有K⁺通道阻断特性。DeHE的血管舒张作用可能涉及多种作用机制，包括内皮依赖性、α1 - 肾上腺素能受体阻断、K⁺通道激活和Ca²⁺通道阻断。
