（-）Doxazosin is a necessary component for the hypotensive effect of （±）doxazosin during long-term administration in conscious rats  

作　　者：Jing ZHAO De-zhi KONG Qing LI Ya-qin ZHEN Miao WANG Yan ZHAO Dong-kai WANG Lei-ming REN 

机构地区：[1]Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China

出　　处：《Acta Pharmacologica Sinica》2014年第1期48-57,共10页中国药理学报（英文版）

摘　　要：Aim： Doxazosin is a racemic mixture of （–）doxazosin and （＋）doxazosin that is currently used as an add-on therapy for hypertension. In this study we investigated the contribution of each enantiomer to the hypotensive action of long-term administration of （±）doxazosin in conscious rats. Methods： Blood pressure of conscious SD rats was measured using a volume pressure recording system. The rats were orally administered （–）doxazosin, （＋）doxazosin, or （±）doxazosin （8 mg·kg-1·d-1） for 12 weeks. Plasma concentrations of the agents were analyzed with HPLC. The effect of the agents on α1-adrenoceptor was examined in isolated rat caudal artery preparations. Results： Treatment of conscious rats with a single dose of （±）doxazosin （8 mg/kg） did not affected DBP and MBP, but significantly decreased SBP by 11.9% 4 h after the administration. Long-term treatment of conscious rats with （±）doxazosin significantly decreased SBP, DBP and MBP with a maximal decrease of SBP by 29.3% 8 h after the last administration. The rank order of the hypotensive actions caused by long-term treatment in conscious rats was （±）doxazosin〉（＋）doxazosin〉〉（–）doxazosin. However, the pKB values for inhibiting NA-induced contraction of isolated rat caudal artery were （＋）doxazosin （8.995）〉（±）doxazosin （8.694）〉（–）doxazosin （8.032）. The plasma concentrations of （–）doxazosin, （＋）doxazosin, and （±）doxazosin were 18.26±3.55, 177.11±20.66, and 113.18±13.21 ng/mL, respectively, 8 h after the last administration of these agents. Conclusion： Long-term treatment with （±）doxazosin produces potent hypotensive action in conscious rats that seems to result from synergic interaction of the two enantiomers.Aim： Doxazosin is a racemic mixture of （–）doxazosin and （＋）doxazosin that is currently used as an add-on therapy for hypertension. In this study we investigated the contribution of each enantiomer to the hypotensive action of long-term administration of （±）doxazosin in conscious rats. Methods： Blood pressure of conscious SD rats was measured using a volume pressure recording system. The rats were orally administered （–）doxazosin, （＋）doxazosin, or （±）doxazosin （8 mg·kg-1·d-1） for 12 weeks. Plasma concentrations of the agents were analyzed with HPLC. The effect of the agents on α1-adrenoceptor was examined in isolated rat caudal artery preparations. Results： Treatment of conscious rats with a single dose of （±）doxazosin （8 mg/kg） did not affected DBP and MBP, but significantly decreased SBP by 11.9% 4 h after the administration. Long-term treatment of conscious rats with （±）doxazosin significantly decreased SBP, DBP and MBP with a maximal decrease of SBP by 29.3% 8 h after the last administration. The rank order of the hypotensive actions caused by long-term treatment in conscious rats was （±）doxazosin〉（＋）doxazosin〉〉（–）doxazosin. However, the pKB values for inhibiting NA-induced contraction of isolated rat caudal artery were （＋）doxazosin （8.995）〉（±）doxazosin （8.694）〉（–）doxazosin （8.032）. The plasma concentrations of （–）doxazosin, （＋）doxazosin, and （±）doxazosin were 18.26±3.55, 177.11±20.66, and 113.18±13.21 ng/mL, respectively, 8 h after the last administration of these agents. Conclusion： Long-term treatment with （±）doxazosin produces potent hypotensive action in conscious rats that seems to result from synergic interaction of the two enantiomers.

关 键 词：DOXAZOSIN ENANTIOMER blood pressure HYPOTENSION plasma drug concentration Α1-ADRENOCEPTOR NORADRENALINE tail artery conscious rat 

分 类 号：O657.1[理学—分析化学] S789.4[理学—化学]