| Benign prostatic hyperplasia (BPH) is one of the mostcommon diseases in elder men. a1-Adrenocepter antagonists caninhibit the over-contraction of the smooth muscle in the prostate,urethral tract and bladder neck, and improve the urinarydynamics of BPH patients and their clinical symptoms.a1-Adrenocepter antagonists, however, are limited in thetreatment of BPH because its cardiovascular side effects. It isimpotant to develop the highly selective a1-Adrenocepterantagonist to the lower urinary tract.Objective: To observe the effects of doxazosin enantiomerson the function of the rat isolated atrium and ventricle, and theeffects on the contractile and relaxant responses of the guineapig isolated trachea smooth muscle.Methods: The rat isolated right atrium, left atrium and rightventricle strip were prepared, and doxazosin enantiomers at 3,10, 30μmol·L-1 were cumulatively applied to the rat isolatedatrium preparation, while doxazosin enantiomers werenoncumulatively applied to the rat isolated right ventriclepreparation. Effects of doxazosin enantiomers on thecontractile force and heart rate were observed. The guinea pig isolated tracheal rings were prepared, andcarbachol or isoprenaline was cumulatively applied to the theguinea pig isolated tracheal rings pretreated with 30μmol·L-1doxazosin enantiomers. Effects of doxazosin enantiomers onthe resting tension, contractile response to carbachol andrelaxant response to isoprenaline were observed in the guineapig isolated tracheal smooth muscle.Results:1 Effects of doxazosin enantiomers on heart rate in the ratisolated right atriumS-Doxazosin at 3～10μmol·L-1 did not induce cardiac arrest,while R-doxazosin and rac-doxazosin induced cardiac arrest by28% and 7%.S-Doxazosin at 3～30μmol·L-1 did not affect the heart rate ofthe rat isolated right atrium, while R-doxazosinconcentration-dependently decreased the heart rate and themaximal decrease by R-doxazosin at 30μmol·L-1 was35.7±21.2%. rac-Doxazosin at 30μmol·L-1 decreased the heartrate of the rat isolated right atrium by 15.7±22.6%.2 Effects of doxazosin enantiomers on the contractile force inthe rat isolated left atriumS-Doxazosin at 3～30μmol·L-1 concentration-dependentlyincreased the contractile force of the rat isolated left atrium,and it increased the contractile force by 50.4±19.7% at30μmol·L-1. R-Doxazosin at the same concentration decreasedthe contractile force of the rat isolated left atrium in concentration dependent manner, and the maximal decrease byR-doxazosin at 30μmol·L-1 was 60.5±17.4%. rac-Doxazosindecreased the contractile force of the rat isolated left atrium by45.7±18.4% at 30μmol·L-1.3 Effects of doxazosin enantiomers on the contractile force inthe rat isolated right ventricle stripS-Doxazosin at 3～30μmol·L-1 had no effect on the contractileforce of the rat isolated right ventricle strip, while R-doxazosinand rac-doxazosin concentration-dependently decreased thecontractile force of the rat isolated right ventricle strip, andR-doxazosin and rac-doxazosin at 30μmol·L-1 decreased thecontractile force by 87.6±6.2% and 70.9±10.2% respectively.4 Effects of doxazosin enantiomers on the resting tension of theguinea pig isolated trachea smooth muscleNo effects of doxazosin enantiomers at 30μmol·L-1 on theresting tension of the guinea pig isolated trachea smoothmuscle were observed.5 Effects of doxazosin enantiomers on the contractile responsesto carbachol in the guinea pig isolated trachea smooth muscleS-Doxazosin at 30μmol·L-1 significantly increased the Emaxof the contractile response to carbachol in the guinea pigisolated trachea smooth muscle, but did not affect the EC50 ofcarbachol.6 Effects of doxazosin enantiomers on the relaxant responses toisoprenaline in the guinea-pigs isolated trachea smooth muscleS-Doxazosin, R-doxazosin and rac-doxazosin (30μmol·L-1) had no effect on the relaxant responses to isoprenaline in theguinea pig isolated trachea smooth muscle.Conclusion: rac-Doxazosin at 3～10μmol·L-1 induces cardiacarrest and significantly reduces the contractile force in the ratisolated right ventricle, and the heart toxicity ofrac-doxazosin is related to R-doxazosin. S-Doxazosin at thesame concentration does not induce cardiac toxicity.S-Doxazosin at 30μmol·L-1 increases the contractileresponses to carbachol in the guinea pig isolated tracheasmooth muscle significantly, but it does not affect the EC50 ofcarbachol acting on muscarinic receptors. Doxazosinenantiomers at 30μmol·L-1 have no effects on the relaxantresponses to isoprenaline in the same preparation.
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