title: (-)Doxazosin is a necessary component for the hypotensive effect of (±)doxazosin during long-term administration in conscious rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Long-term treatment with (±)doxazosin produces potent hypotensive action in conscious rats that seems to result from synergic interaction of the two enantiomers.
authors: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors: Jing
authors: J
authors: Zhao
authors: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors: De-zhi
authors: DZ
authors: Kong
authors: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors: Qing
authors: Q
authors: Li
authors: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors: Ya-qin
authors: YQ
authors: Zhen
authors: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors: Miao
authors: M
authors: Wang
authors: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors: Yan
authors: Y
authors: Zhao
authors: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors: Dong-kai
authors: DK
authors: Wang
authors: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors: Lei-ming
authors: LM
authors: Ren
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003243:Consciousness / Q000187:drug effects* / Q000502:physiology; D017292:Doxazosin / Q000008:administration & dosage* / Q000097:blood; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000959:Antihypertensive Agents; D017292:Doxazosin