Sadeghipour Hamed, Ghasemi Mehdi, Nobakht Maliheh, Ebrahimi Farzad, Dehpour Ahmad Reza
Department of Pharmacology, School of Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
BJU Int. 2007 Jan;99(1):177-82. doi: 10.1111/j.1464-410X.2006.06530.x. Epub 2006 Oct 11.
To verify the effect of chronic lithium administration on the endothelium-dependent relaxation of rat corpus cavernosum, as lithium is a major drug for treating bipolar disorder and some studies showed that lithium might cause erectile dysfunction in such patients, by a mechanism as yet unknown.
LiCl (600 mg/L) was dissolved in drinking water and Sprague-Dawley rats received the solution for 30 days; control rats received tap water. After 30 days corporeal strips were prepared from both groups, mounted under tension in oxygenated organ baths, and pre-contracted with phenylephrine (7.5 microm). After equilibration, the strips were relaxed by acetylcholine (10 nm to 1 mm) in the presence or absence of indomethacin (a cyclooxygenase inhibitor; 20 microm). Furthermore, the relaxant responses to sodium nitroprusside (1 nm to 1 mm), a nitric oxide (NO) donor, were investigated in both groups. NADPH-diaphorase histochemistry was used to identify NO synthase within cavernosal tissue strips of both groups.
The acetylcholine-dependent relaxation was significantly lower in lithium-treated rats than in controls. Although indomethacin decreased significantly the relaxant responses to acetylcholine in controls, it increased the relaxant responses in lithium-treated rats. NADPH-diaphorase staining was greater in the chronic lithium-treated than in control preparations. Sodium nitroprusside produced similar relaxation in both groups.
Chronic lithium administration can impair the endothelium-dependent relaxation of rat corpus cavernosum; NO availability might decrease after lithium administration and the cyclooxygenase pathways might have a role in this effect.
验证长期给予锂盐对大鼠海绵体内皮依赖性舒张功能的影响，因为锂盐是治疗双相情感障碍的主要药物，且一些研究表明锂盐可能会导致此类患者出现勃起功能障碍，但其机制尚不清楚。
将LiCl（600mg/L）溶解于饮用水中，Sprague-Dawley大鼠饮用该溶液30天；对照大鼠饮用自来水。30天后，从两组大鼠制备海绵体条带，置于充满氧气的器官浴槽中并施加张力，用去氧肾上腺素（7.5微摩尔）进行预收缩。平衡后，在有或无吲哚美辛（一种环氧化酶抑制剂；20微摩尔）存在的情况下，用乙酰胆碱（10纳米至1毫米）使条带舒张。此外，还研究了两组对一氧化氮（NO）供体硝普钠（1纳米至1毫米）的舒张反应。采用NADPH-黄递酶组织化学法鉴定两组海绵体组织条带中的NO合酶。
锂处理组大鼠的乙酰胆碱依赖性舒张明显低于对照组。虽然吲哚美辛显著降低了对照组对乙酰胆碱的舒张反应，但却增加了锂处理组大鼠的舒张反应。慢性锂处理组的NADPH-黄递酶染色比对照组更强。硝普钠在两组中产生的舒张作用相似。
长期给予锂盐可损害大鼠海绵体的内皮依赖性舒张功能；给予锂盐后NO的可用性可能降低，环氧化酶途径可能在此效应中起作用。
