Soukhova-O'Hare Galia K, Shah Zahoor A, Lei Zhenmin, Nozdrachev Alexander D, Rao C Venkateswara, Gozal David
Kosair Children's Hospital Research Institute, University of Louisville, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA.
Am J Respir Crit Care Med. 2008 Sep 15;178(6):644-50. doi: 10.1164/rccm.200801-190OC. Epub 2008 Jun 5.
Erectile dysfunction (ED) is frequent in obstructive sleep apnea syndrome (OSAS). Chronic intermittent hypoxia (CIH), one of the hallmarks of OSAS, could mediate ED.
To determine whether intermittent hypoxia during sleep affects erectile dysfunction in mice.
Three groups of C57BL/6 mice were exposed to CIH for 5 or 24 weeks. Sexual function was evaluated by in vivo telemetry of corpus spongiosum pressure. Spontaneous erections, sexual activity during mating, and noncontact tests were assessed after 5 weeks of CIH and after treatment with tadalafil. Plasma testosterone was measured after 8 and 24 weeks of CIH, and the expression of nitric oxide synthase (NOS) isoforms was examined in penile tissue.
Noncontact, spontaneous, and contact sexual activity in the mice was suppressed after CIH. Spontaneous erection counts decreased after the first week of CIH by 55% (P < 0.001) and remained unchanged thereafter. Recovery of erectile activity during normoxia for 6 weeks was incomplete. Compared with control mice, latencies for mounts and intromissions increased by 60- and 40-fold, respectively (P < 0.001), and the sexual activity index decreased sixfold. Tadalafil treatment significantly attenuated these effects. Immunoblot analyses of NOS proteins in the erectile tissue showed decreased expression of endothelial NOS after CIH (P < 0.01), with no changes in plasma testosterone levels after 8 and 24 weeks of CIH.
CIH during sleep is associated with decreased libido in mice. The decreased expression of endothelial NOS protein in erectile tissue and the favorable response to tadalafil suggest that altered nitric oxide mechanisms underlie CIH-mediated ED. No changes in testosterone emerge after intermittent hypoxia.
勃起功能障碍（ED）在阻塞性睡眠呼吸暂停综合征（OSAS）中很常见。慢性间歇性缺氧（CIH）是OSAS的主要特征之一，可能介导ED。
确定睡眠期间的间歇性缺氧是否会影响小鼠的勃起功能障碍。
将三组C57BL/6小鼠暴露于CIH环境中5周或24周。通过海绵体压力的体内遥测评估性功能。在CIH处理5周后以及用他达拉非治疗后，评估自发勃起、交配期间的性活动和非接触测试。在CIH处理8周和24周后测量血浆睾酮，并检测阴茎组织中一氧化氮合酶（NOS）同工型的表达。
CIH后小鼠的非接触、自发和接触性活动均受到抑制。CIH第一周后自发勃起次数减少了55%（P<0.001），此后保持不变。常氧6周期间勃起活动的恢复不完全。与对照小鼠相比，骑跨和插入潜伏期分别增加了60倍和40倍（P<0.001），性活动指数下降了6倍。他达拉非治疗显著减轻了这些影响。勃起组织中NOS蛋白的免疫印迹分析显示，CIH后内皮型NOS表达降低（P<0.01），CIH处理8周和24周后血浆睾酮水平无变化。
睡眠期间的CIH与小鼠性欲降低有关。勃起组织中内皮型NOS蛋白表达降低以及对他达拉非的良好反应表明，一氧化氮机制改变是CIH介导的ED的基础。间歇性缺氧后睾酮水平无变化。
