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.
Similar content being viewed by others
Article PDF
References
Lepor H, Baumann M, Shapiro E . Binding and functional properties of doxazosin in the human prostate adenoma and canine brain. Prostate 1990; 16: 29–38.
Perlberg S, Caine M . Adrenergic response of bladder muscle in prostatic obstruction. Its relation to detrusor instability. Urology 1982; 20: 524–7.
Hatano A, Tang R, Walden PD, Lepor H . The α-adrenoceptor antagonist properties of the enantiomers of doxazosin in human prostate. Eur J Pharmacol 1996; 313: 135–43.
Yang ZH, Ren LM, Wu ZJ, Fu SX, Li YS . Selective effects of alfuzosin and doxazosin with intraduodenal administration on urethral pressure of cats. Acta Pharmacol Sin 1999; 20: 431–4.
Niu CQ, Zhao D, Jia XM, Ren LM . α1-Adrenoceptor antagonist profile of doxazosin and its enantiomers in isolated rabbit blood vessels. Chin J Pharmacol Toxicol 2003; 17: 354–9.
Sun L, Rao MR, Liu PQ . Effects of praeruptorin C on cardiac dysfunction, myocardial compliance and collagen content in reno-vascular hypertensive rats. Acta Pharm Sin 1997; 32: 578–82.
Myers RA, Plym MJ, Signor LJ, Lodge NJ . 1-(2-pyrimidinyl)-piperazine, a buspirone metabolite, modulates bladder function in the anesthetized rat. Neurourol Urodyn 2004; 23: 709–15.
Angelico P, Velasco C, Guarneri L, Sironi G, Leonardi A, Testa R . Urodynamic effects of oxybutynin and tolterodine in conscious and anesthetized rats under different cystometrographic conditions. BMC Pharmacol 2005; 5: 14.
Tanoue A, Koshimizu TA, Shibata K, Nasa Y, Takeo S, Tsujimoto G . Insights into α1 adrenoceptor function in health and disease from transgenic animal studies. Trends Endocrinol Metab 2003; 14: 107–13.
Chiba S, Tsukada M . Existence of functional α1A- and α1D- but no α1B-adrenoceptor subtypes in rat common carotid arteries. Jpn J Pharmacol 2002; 88: 146–50.
Shen H, Peri KG, Deng XF, Chemtob S, Varma DR . Distribution of alpha 1-adrenoceptor subtype proteins in different tissues of neonatal and adult rats. Can J Physiol Pharmacol 2000; 78: 237–43.
Oades GM, Eaton JD, Kirby RS . The clinical role of alpha-blockers in the treatment of benign prostatic hyperplasia. Curr Urol Rep 2000; 1: 97–102.
Ishizuka O, Persson K, Mattiasson A, Naylor A, Wyllie M, Andersson K . Micturition in conscious rats with and without bladder outlet obstruction: role of spinal alpha1-adrenoceptors. Br J Pharmacol 1996; 117: 962–6.
de Groat WC . Anatomy of the central neural pathways controlling the lower urinary tract. Eur Urol 1998; 34( suppl 1): 2–5.
Somogyi GT, Tanowitz M, de Groat WC . Prejunctional facilitatory alpha1-adrenoceptors in the rat urinary bladder. Br J Pharmacol 1995; 114: 1710–6.
Szell EA, Yamamoto T, de Groat WC, Somogyi GT . Smooth muscle and parasympathetic nerve terminals in the rat urinary bladder have different subtypes of α1 adrenoceptors. Br J Pharmacol 2000; 130: 1685–91.
Author information
Authors and Affiliations
Corresponding author
Additional information
Project supported by the Hebei Natural Science Foundation (No C2006000802).
Rights and permissions
About this article
Cite this article
Ma, Sp., Ren, Lm., Zhao, D. et al. Chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats. Acta Pharmacol Sin 27, 1423–1430 (2006). https://doi.org/10.1111/j.1745-7254.2006.00443.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2006.00443.x
Keywords
This article is cited by
-
(−)Doxazosin is a necessary component for the hypotensive effect of (±)doxazosin during long-term administration in conscious rats
Acta Pharmacologica Sinica (2014)