Effects Of Doxazosin Enantiomers On Blood Pressure And Bladder Pressure In Anesthetized Rats

At present,????1?adrenoceptor antagonists are usually considered as the first-line therapy for benign prostatic hyperplasia (BPH), which decrease urethral pressure and resistance, and improve the urethral obstruction symptoms of BPH. It is well-known that the blockade of ??1?adrenoceptor in cardiovascular system in the treatment of BPH produces several side effects, which limit the clinical use of ??1?adrenoceptor antagonists. Objective: To study the effects of α1adrenoceptor antagonist, doxazosin enantionmers, on the carotid pressure, left ventricular pressure and vesical pressure in anesthetized rats.Method: In anesthetized rats, carotid blood pressure, left ventricular pressure and the vesical pressure were recorded.Results: Doxazosin and its enantiomers were administered intravenously in anesthetized rats. Single dose of R-doxazosin at 0.25, 2.5, 25 and 250nmol/kg produced a stronger inhibition on the carotid systolic, diastolic and mean blood pressure than S-doxazosin, and a slight decrease in heart rate was observed only at the highest dose of S-doxazosin. When doxazosin and its enantiomers were administered accumulatively to the anesthetized rats, the ED30 values of R-doxazosin, S-doxazosin and RS-doxazosin were 15.64, 45.93 and 128.81, respectively, and their ratio was 1:2.94:8.24. Doxazosin and its enantiomers administered accumulatively in anesthetized rats induced a dose-dependent inhibition on the left ventricular (LVSP) and ±dp/dtmax, and a potency order of the three agents was R(+)doxazosin > RS(±)doxazosin > S(?)doxazosin. The inhibitory effect of doxazosin enantiomers on +dp/dtmax was weaker than that on ?dp/dtmax. No significant changes were obsered in the left ventricular end-diastolic pressure (LVEDP) in anesthetized rats administered doxazosin and its enantiomers. Single dose of doxazosin and its enantiomers decreased the vesical micturation pressure (MP) dose-dependently at the 2.5, 25 and 250 nmol/kg, and the inhibitory potency among the three agents was same. However, they had no significant effect on the basal pressure (BP), interconstraction interval (ICI) and micturation volume (MV).Conclusion: Doxazosin and its enantiomers similarly decreased micturation pressure of bladder. However, S-doxazosin produced the weaker inhibition on the blood pressure and left ventricular pressure than R-doxazosin and RS-doxazosin.