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醋酸铅、硫酸铝和硫酸镉对大鼠海绵体作用的不同机制。

Different mechanisms for lead acetate, aluminum and cadmium sulfate in rat corpus cavernosum.

作者信息

Senbel Amira M, Saad Evan I, Taha Safaa S, Mohamed Hosny F

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.

出版信息

Toxicology. 2016 Jan 18;340:27-33. doi: 10.1016/j.tox.2015.12.004. Epub 2015 Dec 23.

Abstract

INTRODUCTION

Some heavy metals show adverse vascular and neurological effects, however, their effect on erection is underestimated. This study aims to investigate the effect of Pb, Cd and Al on erectile function and their potential mechanism of action in rats.

METHODS

Measurement of intracavernosal pressure/mean arterial pressure (ICP/MAP) changes elicited by electrical stimulation of cavernous nerve in anesthetized rats treated with Pb-acetate, Al-sulfate, or Cd-sulfate acutely, and subacutely for 7 days. Serum creatinine, testosterone, TBARs, GSH levels and metal accumulation in corpus cavernosum were measured.

RESULTS

Pb, Al and Cd significantly reduced ICP/MAP in rats after acute (2,10-2,10 and 1,3 mg/kg respectively) and sub-acute (3, 3, and 1mg/kg/day respectively) treatments. They selectively accumulated in the corpus cavernosum reaching 25.107 ± 2.081 μg/g wet weight for Pb, 1.029 ± 0.193 for Cd, 31.343 ± 1.991 for Al, compared to 7.084 ± 1.517, 0.296 ± 0.067, and 8.86 ± 1.115 as controls respectively. Serum creatinine levels were not altered. Cd and Al significantly reduced testosterone level to 0.483 ± 0.059 and 0.419 ± 0.037 ng/ml respectively compared to 0.927 ± 0.105 ng/ml as control. Aluminum elevated TBARs significantly by 27.843%. The acute anti-erectile action of Pb was blocked by non-selective NOS and GC inhibitors and potassium channel blocker. Lead also masked the potentiatory effect of l-arginine and diazoxide on ICP/MAP. No interaction with muscarinic or nicotinic modulators was observed.

CONCLUSIONS

Pb, Cd and Al show anti-erectile effect independent on renal injury. They don not modulate cholinergic nor ganglionic transmission in corpus cavernosum. Pb may inhibit NO/cGMP/K+channel pathway. The effect of Cd and Al but not Pb seems to be hormonal dependent.

摘要

引言

一些重金属会对血管和神经系统产生不良影响,然而,它们对勃起功能的影响却被低估了。本研究旨在探讨铅、镉和铝对大鼠勃起功能的影响及其潜在作用机制。

方法

对急性及亚急性(持续7天)给予醋酸铅、硫酸铝或硫酸镉处理的麻醉大鼠,通过电刺激海绵体神经来测量海绵体内压/平均动脉压(ICP/MAP)的变化。检测血清肌酐、睾酮、丙二醛(TBARs)、谷胱甘肽(GSH)水平以及海绵体内的金属蓄积情况。

结果

急性处理(铅、铝、镉分别为2.10 - 2.10和1.3mg/kg)及亚急性处理(分别为3、3和1mg/kg/天)后,铅、铝和镉均显著降低大鼠的ICP/MAP。它们选择性地蓄积于海绵体中,铅达到25.107±2.081μg/g湿重,镉为1.029±0.193,铝为31.343±1.991,而对照组分别为7.084±1.517、0.296±0.067和8.86±1.115。血清肌酐水平未发生改变。与对照组0.927±0.105ng/ml相比,镉和铝分别显著降低睾酮水平至0.483±0.059和0.419±0.037ng/ml。铝使TBARs显著升高27.843%。非选择性一氧化氮合酶(NOS)和鸟苷酸环化酶(GC)抑制剂以及钾通道阻滞剂可阻断铅的急性抗勃起作用。铅还掩盖了L - 精氨酸和二氮嗪对ICP/MAP的增强作用。未观察到与毒蕈碱或烟碱调节剂的相互作用。

结论

铅、镉和铝显示出独立于肾损伤的抗勃起作用。它们不调节海绵体内的胆碱能或神经节传递。铅可能抑制一氧化氮/环磷酸鸟苷/钾通道途径。镉和铝而非铅的作用似乎依赖于激素。

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