title: Relaxant and contractile responses of detrusor muscle strips obtained from bladder outlet-obstructed rats treated with doxazosin enantiomers.
abstract: (-)Doxazosin, one of (±)doxazosin enantiomers, was speculated to have a pharmacological enantioselectivity between the cardiovascular system and the urinary system by comparison with (+)doxazosin. Therefore, to evaluate the potential benefits of (-)doxazosin in the treatment of benign prostate hyperplasia, we compared the effects of the 3 agents, using rat mesenteric artery preparations and obstructed bladder strips. Concentration-response curves for carbachol (contractile response) and isoprenaline (relaxant response) in detrusor muscle strips of the bladder outlet obstruction (BOO) rats were shifted to the left, with significant increases in the Emax values, and significant decreases in the EC50 values by comparison with the sham-operated rats (P < 0.05, n = 10). The enhanced responses in detrusor muscle strips of the BOO rats treated with (±)doxazosin and its enantiomers at 3 mg·(kg body mass)(-1)·day(-1) for 2 weeks returned to normal levels, and the 3 agents inhibited the enhanced responses to carbachol and isoprenaline to the same extent. On the other hand, the 3 agents uncompetitively inhibited the vasoconstrictive response curves for NA in the rat isolated mesenteric artery, and the pKB value of (-)doxazosin at vascular α1-adrenoceptors was significantly smaller (P < 0.05, n = 6) than that of (+)doxazosin or (±)doxazosin. In conclusion, although (-)doxazosin inhibits vascular functional α1-adrenoceptors more weakly than (+)doxazosin, both agents equally ameliorate the enhanced responses in detrusor muscle of BOO rats, suggesting that the chiral carbon atom in the molecular structure of doxazosin does not affect its beneficial effects in the bladder smooth muscle of BOO rats.
authors: a Institute of Chinese Integrative Medicine, Hebei Medical University, 361 East Zhong-shan Road, Shijiazhuang 050017, Hebei, P. R. China.
authors: Miao
authors: M
authors: Wang
authors: Xue-Jiao
authors: XJ
authors: Ren
authors: Qing-Hua
authors: QH
authors: Zhao
authors: Li-Xin
authors: LX
authors: Lin
authors: Xue
authors: X
authors: Wang
authors: Yan
authors: Y
authors: Zhao
authors: Lei-Ming
authors: LM
authors: Ren
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D017292:Doxazosin / Q000737:chemistry / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology; D017208:Rats, Wistar; D013237:Stereoisomerism; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000503:physiopathology*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D018679:Cholinergic Agonists; D002217:Carbachol; D007545:Isoproterenol; D017292:Doxazosin; D009638:Norepinephrine