Chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats

• Published in: Acta pharmacologica Sinica Vol. 27; no. 11; pp. 1423 - 1430
• Main Authors: Ma, Shi-ping, Ren, Lei-ming, Zhao, Ding, Zhu, Zhong-ning, Wang, Miao, Liu, Hai-gang, Duan, Li-hua
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.11.2006
• Subjects: Adrenergic alpha-Antagonists - administration & dosage; Adrenergic alpha-Antagonists - pharmacology; Animals; Blood Pressure - drug effects; Dose-Response Relationship, Drug; Doxazosin - administration & dosage; Doxazosin - pharmacology; Heart Rate - drug effects; Male; Pressure; Rats; Rats, Wistar; Stereoisomerism; Urinary Bladder - drug effects; Urinary Bladder - physiology; Ventricular Pressure - drug effects; 对映体
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1111/j.1745-7254.2006.00443.x

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 ED30 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. Conclusion： S-doxazosin decreases the carotid blood pressure and left ventricular pressure of the heart less than R-doxazosin and racdoxazosin, 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.