多沙唑嗪对映体诱发大鼠心房肌收缩力变化的作用机制

摘要

目的：分析多沙唑嗪对映体的手性结构诱发大鼠离体心房肌收缩力变化的作用机制。方法建立（－）DOX诱发的大鼠离体左心房正性肌力模型以及（＋）DOX诱发的大鼠离体左心房负性肌力模型，探讨DOX对映体诱发大鼠心房肌正性肌力作用或负性肌力作用的机制。结果在维拉帕米预处理标本，3μmol·L－1浓度（－）DOX的正性肌力作用由对照组的（245.71±44.29）mg降低至（172.50±43.34） mg（P＜0.05）。在亚甲蓝预处理标本，3μmol · L－1浓度（－）DOX的正性肌力作用由对照组的（245.7 1±44.29）mg增强至（303.33±45.90）mg（P＜0.05）。在H-89预处理标本，3、10和30μmol·L－1（－）DOX诱发的正性肌力作用由对照组的（245.71±44.29）mg、（314.29±90.34）mg 和（357.14±68.49）mg增强至（338.57±96.86）mg、（471.43±107.61）mg和（520.00±103.44）mg（P＜0.05或0.01）。酚苄明、阿托品、普萘洛尔、吲哚美辛预处理标本时，多沙唑嗪对映体的未见明显改变。结论（－）DOX增强大鼠心房肌收缩力的作用，可能与心肌α受体、M胆碱受体、β受体以及环氧合酶无关；L型Ca2＋通道以及细胞内cGMP可能在某种程度上参与了（－）DOX在大鼠左心房的正性肌力作用。但是，心肌α受体、M胆碱受体、β受体、Ca2＋通道、环氧合酶、cGMP及PKA，可能未参与（＋）DOX对大鼠左心房的负性肌力作用。%Aim To study the mechanisms of inotropic responses to doxazosin enantiomers in the isolated rat atrium.Methods We analyzed the positive inotropic response to (-)doxazosin and the negative inotropic response to (+)doxazosin in the left atrium of rat u-sing receptor-pharmacological technique.Results In the preparation treated with verapamil,the positive in-otropic responses to 3 μmol·L-1 (-)doxazosin were significantly inhibited from the control level (245.7 1 ± 44.29)mg to (172.50 ±43.34)mg,(P<0.05).In the preparation treated with methylene blue,the posi-tive inotropic responses to 3 μmol·L-1 (-)doxazosin were significantly potentiated from the control level (245.7 1 ±44.29 )mg to (303.33 ±45 .90 )mg,(P<0.05 ).In the preparation treated with H-89 ,the positive inotropic responses to 3,10 and 30 μmol · L-1 (-)doxazosin were (338.57 ±96.86 ) mg, (471.43 ±107.61)mg and (520.00 ±103.44)mg, which were significantly (P<0.05 ~0.01)larger than the control levels of (245.71 ±44.29)mg,(314.29 ±90.34)mg and (357.14 ±68.49 )mg.Treatment with phenoxybenzamine,atropine,propranolol or indo-methacin did not significantly affect the responses to doxazosin enantiomers.Conclusion The positive ino-tropic responses to (-)doxazosin in the isolated left a-trium of rat are partially involved in L-type Ca2+chan-nels and intracellular cGMP level.However,α-adre-noceptors,muscarinic receptors,β-adrenoceptors and cyclooxygenases are not related to the responses to doxazosin enantiomers.