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（-）Doxazosin is a necessary component for the hypotensive effect of （±）doxazosin during long-term administration in conscious rats
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（-）Doxazosin is a necessary component for the hypotensive effect of （±）doxazosin during long-term administration in conscious rats
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Journal Article
（-）Doxazosin is a necessary component for the hypotensive effect of （±）doxazosin during long-term administration in conscious rats
2014
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Antihypertensive Agents - administration & dosage
/ Antihypertensive Agents - blood
/ Biomedical and Life Sciences
/ Blood Pressure - drug effects
/ Consciousness - drug effects
/ Doxazosin - administration & dosage
/ Male
/ Original
/ Rats
/ Vaccine
/ 口服给药
/ 外消旋混合物
/ 多沙唑嗪
/ 大鼠
/ 成分
/ 肾上腺素能受体
/ 降血压作用
/ 高效液相色谱法
