Effects of Spinal and Peripheral Injection of α1A or α1D Adrenoceptor Antagonists on Bladder Activity in Rat Models with or without Bladder Outlet Obstruction
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: Antagonists of α1-adrenergic receptors (α1ARs) relax prostate smooth muscle and relieve voiding and storage symptoms. Recently, increased expression of α1ARs with change of its subtype expression has been proved in bladder outlet obstruction (BOO). To search for the evidence of changes in α1ARs subtype expression and activity in the peripheral and spinal routes, the effects of spinal and peripheral administration of tamsulosin (an α1A/D-selective AR), naftopidil (an α1A/D-selective AR), and doxazosin (non-selective AR) on bladder activity were investigated in a rat model with or without BOO. Methods: A total of 65 female Sprague-Dawley rats were divided into the BOO surgery group (n=47) and the sham surgery group (n=18). After 6 weeks, cystometry was assessed before and after intrathecal and intra-arterial administrations of tamsulosin,naftopidil, and doxazosin. Results: After intra-arterial administrations of all three drugs, bladder capacity (BC) was increased and maximal intravesical pressure (Pmax) was decreased in both BOO and the sham rat models (P<0.05). After intrathecal administration of all three drugs, BC was increased and Pmax was decreased in only the BOO group. The episodes of involuntary contraction in the BOO rat models were decreased by intra-arterial administration (P=0.031). The increase of BC after intrathercal and intra-arterial administrations of α1ARs was significantly greater in the BOO group than in the sham group (P=0.023, P=0.041). In the BOO group, the increase of BC and decrease in Pmax were greater by intra-arterial administration than by intrathecal administration (P=0.035). There were no significant differences of the degrees of changes in the cystometric parameters among the three different α1ARs. Conclusions: Up-regulations of the α1ARs in BOO were observed by the greater increases of BC after α1AR antagonist administrations in the BOO group than in the sham group. However, there were no subtype differences of the α1ARs in functional parameters of bladder activity. In addition, α1ARs also act on the lumbosacral cord which implies that the sensitivity of α1ARs is increased in pathologic models such as BOO. Further evaluation including differential expression of α1ARs in BOO models are need.
Abstract
Purpose: Antagonists of α1-adrenergic receptors (α1ARs) relax prostate smooth muscle and relieve voiding and storage symptoms. Recently, increased expression of α1ARs with change of its subtype expression has been proved in bladder outlet obstruction (BOO). To search for the evidence of changes in α1ARs subtype expression and activity in the peripheral and spinal routes, the effects of spinal and peripheral administration of tamsulosin (an α1A/D-selective AR), naftopidil (an α1A/D-selective AR), and doxazosin (non-selective AR) on bladder activity were investigated in a rat model with or without BOO. Methods: A total of 65 female Sprague-Dawley rats were divided into the BOO surgery group (n=47) and the sham surgery group (n=18). After 6 weeks, cystometry was assessed before and after intrathecal and intra-arterial administrations of tamsulosin,naftopidil, and doxazosin. Results: After intra-arterial administrations of all three drugs, bladder capacity (BC) was increased and maximal intravesical pressure (Pmax) was decreased in both BOO and the sham rat models (P<0.05). After intrathecal administration of all three drugs, BC was increased and Pmax was decreased in only the BOO group. The episodes of involuntary contraction in the BOO rat models were decreased by intra-arterial administration (P=0.031). The increase of BC after intrathercal and intra-arterial administrations of α1ARs was significantly greater in the BOO group than in the sham group (P=0.023, P=0.041). In the BOO group, the increase of BC and decrease in Pmax were greater by intra-arterial administration than by intrathecal administration (P=0.035). There were no significant differences of the degrees of changes in the cystometric parameters among the three different α1ARs. Conclusions: Up-regulations of the α1ARs in BOO were observed by the greater increases of BC after α1AR antagonist administrations in the BOO group than in the sham group. However, there were no subtype differences of the α1ARs in functional parameters of bladder activity. In addition, α1ARs also act on the lumbosacral cord which implies that the sensitivity of α1ARs is increased in pathologic models such as BOO. Further evaluation including differential expression of α1ARs in BOO models are need.
참고문헌 (23)
- Bertaccini A, "Symptoms, bothersomeness and quality of life in patients with LUTS suggestive of BPH", Eur Urol, 40(Suppl 1), pp.13~18 (2001)
- Bylund DB, "International Union of Pharmacology nomenclature of adrenoceptors", Pharmacol Rev, 46, pp.121~136 (1994)
- Malloy BJ, "Alpha1-adrenergic receptor subtypes in human detrusor", J Urol, 160(3 Pt 1), pp.937~943 (1998)
- Smith MS, "Alpha1- adrenergic receptors in human spinal cord: specific localized expression of mRNA encoding alpha1-adrenergic receptor subtypes at four distinct levels", Brain Res Mol Brain Res, 63, pp.254~261 (1999)
- Chen Q, "Function of the lower urinary tract in mice lacking alpha1d-adrenoceptor", J Urol, 174, pp.370~374 (2005)
- Barendrecht MM, "The effect of bladder outlet obstruction on alpha1- and beta-adrenoceptor expression and function", Neurourol Urodyn, 28, pp.349~355 (2009)
- Takei R, "Naftopidil, a novel alpha1-adrenoceptor antagonist, displays selective inhibition of canine prostatic pressure and high affinity binding to cloned human alpha1-adrenoceptors", Jpn J Pharmacol, 79, pp.447~454 (1999)
- Igawa Y, "Micturition and premicturition contractions in unanesthetized rats with bladder outlet obstruction", J Urol, 151, pp.244~249 (1994)
- Tanaka H, "Effect of preemptive treatment of capsaicin or resiniferatoxin on the development of pre-micturition contractions after partial urethral obstruction in the rat", J Urol, 170, pp.1022~1026 (2003)
- Jeong MS, "The role of spinal and peripheral alpha1- and alpha2- adrenoceptors on bladder activity induced by bladder distension in anaesthetized rat", BJU Int, 85, pp.925~931 (2000)
- Sugaya K, "Effects of intrathecal injection of tamsulosin and naftopidil, alpha- 1A and -1D adrenergic receptor antagonists, on bladder activity in rats", Neurosci Lett, 328, pp.74~76 (2002)
- Price DT, "Identification, quantification, and localization of mRNA for three distinct alpha 1 adrenergic receptor subtypes in human prostate", J Urol, 150(2 Pt 1), pp.546~551 (1993)
- Weinberg DH, "Cloning, expression and characterization of human alpha adrenergic receptors alpha 1a, alpha 1b and alpha 1c", Biochem Biophys Res Commun, 201, pp.1296~1304 (1994)
- Hampel C, "Modulation of bladder alpha1-adrenergic receptor subtype expression by bladder outlet obstruction", J Urol, 167, pp.1513~1521 (2002)
- Bouchelouche K, "Increased contractile response to phenylephrine in detrusor of patients with bladder outlet obstruction: effect of the alpha1A and alpha1D-adrenergic receptor antagonist tamsulosin", J Urol, 173, pp.657~661 (2005)
- Yokoyama O, "Improvement in bladder storage function by tamsulosin depends on suppression of C-fiber urethral afferent activity in rats", J Urol, 177, pp.771~775 (2007)
- Birder LA, "Mechanisms of disease: involvement of the urothelium in bladder dysfunction", Nat Clin Pract Urol, 4, pp.46~54 (2007)
- Masuda H, "Reactive oxygen species mediate detrusor overactivity via sensitization of afferent pathway in the bladder of anaesthetized rats", BJU Int, 101, pp.775~780 (2008)
- Freeman WM, "Quantitative RT-PCR: pitfalls and potential", Biotechniques, 26, pp.112~125 (1999)
- Rudner XL, "Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age", Circulation, 100, pp.2336~2343 (1999)
- Cannon TW, "Effects of anesthesia on cystometry and leak point pressure of the female rat", Life Sci, 69, pp.1193~1202 (2001)
- Martin DJ, "Comparative alpha-1 adrenoceptor subtype selectivity and functional uroselectivity of alpha-1 adrenoceptor antagonists", J Pharmacol Exp Ther, 282, pp.228~235 (1997)
- Hieble JP, "Effects of alpha1-adrenoceptor antagonists on agonist and tilt-induced changes in blood pressure: relationships to uroselectivity", Eur J Pharmacol, 373, pp.51~62 (1999)