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

  
@article{APS3627,
	author = {Shi-ping Ma and Lei-ming Ren and Ding Zhao and Zhong-ning Zhu and Miao Wang and Hai-gang Lu and Li-hua Duan},
	title = {Chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats},
	journal = {Acta Pharmacologica Sinica},
	volume = {27},
	number = {11},
	year = {2016},
	keywords = {},
	abstract = {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-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 ±dp/dtmax, 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.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/3627}
}