Chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats.
OBJECTIVE
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-doxazosin were 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 +/-dp/dt(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.


CONCLUSIONS
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.
Ma
Shi-ping
SP
Hebei Medical University School of Pharmacy, Shijiazhuang 050017, China.
Ren
Lei-ming
LM
Zhao
Ding
D
Zhu
Zhong-ning
ZN
Wang
Miao
M
Liu
Hai-gang
HG
Duan
Li-hua
LH
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D017292:Doxazosin / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*; D017725:Ventricular Pressure / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D017292:Doxazosin