硝酸异山梨酯对大鼠膀胱逼尿肌的舒张作用

中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (11): 1248-1251.

硝酸异山梨酯对大鼠膀胱逼尿肌的舒张作用

王占庆, 王金萍, 许景峰, 曾明, 陈艳

北京军区总医院药理科,北京 100700

收稿日期:2011-09-30 修回日期:2011-10-24 出版日期:2011-11-26 发布日期:2011-11-29
作者简介:王占庆,男,博士,主管药师,研究方向:化学药物研究与治疗。Tel: 010-66721604 E-mail: wangzhanqing2049@yahoo.com.cn

Effects of isosorbide dinitrate on contractions of rat urine bladder destrusor in vitro

WANG Zhan-qing, WANG Jin-ping, XU Jing-feng, ZENG Ming, CHEN Yan

Department of Pharmacology, General Hospital of Beijing Military Command, Beijing 100700,China

Received:2011-09-30 Revised:2011-10-24 Online:2011-11-26 Published:2011-11-29

摘要/Abstract

摘要： 目的: 研究硝酸异山梨酯(ISDN)对大鼠离体膀胱逼尿肌螺旋条的舒张作用及可能机制。方法: 采用离体逼尿肌螺旋条浴槽实验方法,以硝苯地平为对照,测定ISDN(10^-6～10^-4 mol/L)对氯化钾(4×10^-2 mol/L)和乙酰胆碱(10^-4 mol/L)预收缩离体膀胱逼尿肌条的平均张力、收缩幅度和频度的影响。用标准试剂盒测定膀胱组织经ISDN(10^-4 mol/L)孵育 1 h 后组织中一氧化氮(NO)和一氧化氮合酶(NOS)的活性。结果: ISDN的中剂量组和高剂量组(10^-5 mol/L 和 10^-4 mol/L)对乙酰胆碱预收缩肌螺旋条的平均张力、收缩幅度和频度均明显降低(P<0.05);ISDN各剂量组对高钾预收缩膀胱逼尿肌条的平均张力、收缩幅度和频度均没有明显影响(P>0.05)。另外,膀胱组织经ISDN孵育后NO的含量和NOS的活性明显升高(P<0.05)。结论: ISDN对乙酰胆碱预收缩的膀胱逼尿肌条有一定舒张作用,其机制可能与ISDN激活NOS,升高NO的含量有关。

关键词: 硝酸异山梨酯, 膀胱逼尿肌, 舒张作用, 一氧化氮合酶, 大鼠

Abstract: AIM: To investigate the dilation effect of isosorbide dinitrate (ISDN) on the rat urine bladder rings.METHODS: The values of the mean contraction tension, maximum amplitude and frequency of rat urine bladder rings were measured. The activity of nitric oxide synthase (NOS) and the content of nitric oxide (NO) were measured in the rat urine bladder tissue pre-incubated with ISDN (10^-4 mol/L) for 1 h.RESULTS: ISDN (10^-5 mol/L, 10^-4 mol/L) could inhibit the mean contractile tension, maximum amplitude and frequency of spontaneous rhythmic contractions of rat urine bladder pre-contracted with ACh (10^-4 mol/L). However, there was no significant change to the rings pre-contracted with KCl (4×10^-4 mol/L). And the activity of NOS and the content of NO were elevated in the rat urine bladder tissue pre-incubated with ISDN.CONCLUSION: ISDN can induce relaxation on rat isolated bladder detrusor muscle rings pre-contracted with ACh, and the mechanism is possibly related to the activation of the nitric oxide synthase and the elevation of NO level.

Key words: Isosorbide dinitrate, Urine bladder detrusor, Dilation, Nitric oxide synthase, Rat

中图分类号:

R965.2

王占庆, 王金萍, 许景峰, 曾明, 陈艳. 硝酸异山梨酯对大鼠膀胱逼尿肌的舒张作用[J]. 中国临床药理学与治疗学, 2011, 16(11): 1248-1251.

WANG Zhan-qing, WANG Jin-ping, XU Jing-feng, ZENG Ming, CHEN Yan. Effects of isosorbide dinitrate on contractions of rat urine bladder destrusor in vitro[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(11): 1248-1251.

参考文献

[1] Mónica FT, Bricola AO, Báu FR, et al. Long-term nitric oxide deficiency causes muscarinic supersensitivity and reduces β3-adrenoceptor-mediated relaxation, causing rat detrusor overactivity [J]. Br J Pharmacol, 2008, 153(8): 1659-1668.
[2] Zhou Q, Satake N, Shibata S. The inhibitory mechanisms of nicorandil in isolated rat urinary bladder and femoral artery [J]. Eur J Pharmacol, 1995, 273(1/2): 153-159.
[3] Yutaka K, Satoru M, Hitoshi M, et al. Inhibitory effects of nicorandil, a KATP channel opener and a nitric oxide donor, on overactive bladder in animal model [J]. BJU Int, 2007, 101(3): 360-365.
[4] 高敏,王玉,汪海. 埃他卡林等三种结构类型的钾通道开放剂对非血管平滑肌舒张作用的选择性[J].中国临床药理学与治疗学,2005, 10(6): 633-636.
[5] Fujiwara M, Andersson K, Persson K. Nitric oxide-induced cGMP accumulation in the mouse bladder is not related to smooth muscle relaxation [J]. Euro J Pharm, 2000, 401(2): 241-250.
[6] Naoki A, Yasuhiko I, Osamu N, et al. Effects of nitric oxide on the primary bladder afferent activities of the rat with and without intravesical acrolein treatment [J]. Euro Urol, 2011, 59(2): 264-271.
[7] Weng TI, Chen WJ, Wu HY, et al. Uropathogenic Escherichia coli alters muscle contractions in rat urinary bladder via a nitric oxide synthase-related signaling pathway [J]. J Infect Dis, 2011, 204(12): 1774-1782.
[8] Ozawa H, Chancellor MB, Jung SK, et al. Effect of intravesical nitric oxide therapy on cyclophosphamide-induced cystitis [J]. J Urol, 1999, 162(6): 2211-2216.
[9] Masuda H, Ogawa T, Kihara K, et al. Effects of anaesthesia on the nitrergic pathway during the micturition reflex in rats [J]. BJU Int, 2007, 100(1): 175-180.
[10] Darblade B, Behr-roussel D, Oger S, et al. Effects of potassium channel modulators on human detrusor smooth muscle myogenic phasic contractile activity: potential therapeutic targets foroveractive bladder [J]. Urology, 2006, 68(2): 442-448.
[11] Dilip KD, Alison FB. Nitric oxide activates glibenclamide-sensitive K⁺ channels in urinary bladder myocytes through a c-GMP-dependent mechanism [J]. Euro J Pharm, 2004, 492(1): 13-19.

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