Open AccessChiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats 1
Author(s) -
MA Shiping,
REN Leiming,
ZHAO Ding,
ZHU Zhongning,
WANG Miao,
LU Haigang,
DUAN Lihua
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00443.x
Subject(s) - doxazosin , enantiomer , blood pressure , urinary system , urinary bladder , pharmacology , urology , chemistry , medicine , endocrinology , stereochemistry
Aim: To study chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats. Methods: In anesthetized rats, the carotid blood pressure, left ventricular pressure of the heart and the urinary bladder pressure were recorded. Results: Administration of S ‐doxazosin at 0.25, 2.5, 25, and 250 nmol/kg iv produced a dose‐dependent decrease in blood pressure, but its depressor effect was significantly weaker than that induced by R ‐doxazosin and racemic‐doxazosin (rac‐doxazosin), and the ED 30 values (producing a 30% decrease in mean arterial pressure) of R ‐doxazosin, rac‐doxazosin and S ‐doxazosinwere 15.64,45.93, and 128.81, respectively. Rac‐doxazosin and its enantiomers administered cumulatively in anesthetized rats induced a dose‐dependent decrease in the left ventricular systolic pressure and ±d p /d t max , and the potency order of the 3 agents was R ‐doxazosin >rac‐doxazosin > S ‐doxazosin. Rac‐doxazosin and its enantiomers decreased the vesical micturition pressure dose‐dependently at 2.5,25, and 250 nmol/kg, and the inhibitory potency among the 3 agents was not significantly different. Conclusion: S ‐doxazosin decreases the carotid blood pressure and left ventricular pressure of the heart less than R ‐doxazosin and rac‐doxazosin, but its effect on the vesical micturition pressure is similar to R ‐doxazosin and rac‐doxazosin, indicating that S ‐doxazosin has chiral selectivity between cardiovascular system and urinary system in anesthetized rats.