In:
Canadian Journal of Physiology and Pharmacology, Canadian Science Publishing, Vol. 89, No. 12 ( 2011-12), p. 883-890
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 E max values, and significant decreases in the EC 50 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 pK B value of (–)doxazosin at vascular α 1 -adrenoceptors was significantly smaller (P 〈 0.05, n = 6) than that of (+)doxazosin or (±)doxazosin. In conclusion, although (–)doxazosin inhibits vascular functional α 1 -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.
Type of Medium:
Online Resource
ISSN:
0008-4212
,
1205-7541
Language:
English
Publisher:
Canadian Science Publishing
Publication Date:
2011
detail.hit.zdb_id:
2004356-9
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