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醋酸铅可能通过调节大鼠海绵体中的 NO/cGMP 通路引起勃起功能障碍。

Lead acetate may cause erectile dysfunction by modulating NO/cGMP pathway in rat corpus cavernosum.

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Azarita, P. Box: 21521, Alexandria, Egypt,

出版信息

Cell Biol Toxicol. 2013 Oct;29(5):355-64. doi: 10.1007/s10565-013-9258-x. Epub 2013 Aug 25.

DOI:10.1007/s10565-013-9258-x
PMID:23979109
Abstract

Despite the fact that metal toxicity has been widely reported in industrial toxicological studies, very little has been reported about the effect of lead exposure on erectile function. This study investigated the effect of lead on erectile function in rats and aimed to preliminarily test the mechanisms by which it might affect erection. Rats were injected with lead acetate (0.25-2 mg/kg) intraperitoneally for 21 days. Intracavernosal pressure/mean arterial pressure (ICP/MAP) next to nerve stimulation; nitrite/nitrate; malonaldehyde; and reduced glutathione levels and superoxide dismutase activity in the corpus cavernosum, kidney, and brain were measured in addition to creatinine, urea, and testosterone. For acute studies, rats were injected intravenously with lead acetate, and then ICP/MAP was recorded for 45 min. Subacute treatment significantly reduced erection with significant elevation of malonaldehyde and reduction of nitrite/nitrate levels in the corpus cavernosum. In acute studies, lead (2 and 5 mg/kg) reduced neurogenic erections by 28.42 ± 3.76 and 96.84 ± 8.52%, respectively, an effect that was masked in the presence of NG-nitro-L-arginine, tetraethyl ammonium, or methylene blue, but not zinc protoporphyrine, and reversed by vitamin C and partially by sildenafil. Lead acetate may inhibit the erectile process in rats. Besides its prooxidant effect and consequent inactivation of nitric oxide, lead may negatively modulate the action of nitric oxide on guanylate cyclase and potassium channels.

摘要

尽管金属毒性在工业毒理学研究中已被广泛报道,但关于铅暴露对勃起功能的影响却鲜有报道。本研究旨在探讨铅对大鼠勃起功能的影响,并初步探讨其影响勃起的可能机制。大鼠腹腔内注射醋酸铅(0.25-2 mg/kg)21 天。测量了阴茎海绵体的神经刺激下的腔内压/平均动脉压(ICP/MAP)、硝酸盐/亚硝酸盐、丙二醛;以及还原型谷胱甘肽水平和超氧化物歧化酶活性,同时还测量了肌酐、尿素和睾酮。在急性研究中,大鼠静脉内注射醋酸铅,然后记录 45 分钟的 ICP/MAP。亚急性治疗显著降低了勃起功能,同时显著增加了阴茎海绵体中的丙二醛含量,降低了硝酸盐/亚硝酸盐水平。在急性研究中,铅(2 和 5 mg/kg)分别使神经源性勃起降低了 28.42±3.76%和 96.84±8.52%,这种作用在存在 NG-硝基-L-精氨酸、四乙铵或亚甲蓝时被掩盖,但在锌原卟啉存在时不被掩盖,维生素 C 和西地那非部分逆转了这种作用。醋酸铅可能抑制大鼠的勃起过程。除了其促氧化作用和由此导致的一氧化氮失活外,铅可能还会负性调节一氧化氮对鸟苷酸环化酶和钾通道的作用。

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