da Silva Júnior E D, de Souza B P, Vilela V V, Rodrigues J Q D, Nichi M, de Agostini Losano J D, Dalmazzo A, Barnabe V H, Jurkiewicz A, Jurkiewicz N H
Department of Pharmacology, Mechanism of Drug Action Laboratory, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
Andrology. 2014 Nov;2(6):955-66. doi: 10.1111/andr.283. Epub 2014 Oct 1.
The use of clonidine, a selective agonist of α2-adrenoceptors, is related to the fertility impairment. Thus, it has been described that changes in the epididymal function are related to the loss of fertility. Therefore, this study was sought to further evaluate the effects of clonidine in the rat distal cauda epididymis contractions and its consequence in the sperm parameters. The in vitro effects of clonidine in the isolated distal cauda epididymis were evaluated by pharmacological experiments. The consecutive contractile responses for clonidine in distal cauda epididymis showed desensitization. The noradrenaline-induced contractions were desensitized after in vitro clonidine pre-treatment (10(-5) M for 10 min). Clonidine was unable to alter the noradrenaline contractions if the in vitro pre-treatment was made in the presence of idazoxan (α2-adrenoceptor antagonist), whereas prazosin (α1-adrenoceptor antagonist) was ineffective. Moreover, the in vitro clonidine pre-treatment increased frequency and amplitude of spontaneous contraction of distal cauda epididymis. In addition, to induce in vivo desensitization of α2-adrenoceptors, male Wistar rats were treated with crescent doses of clonidine and distal cauda of epididymis contraction and sperm parameters were analyzed. The in vivo treatment with clonidine diminished the potency of the contractions induced by adrenergic agonists and augmented the frequency and amplitude of spontaneous contraction of distal cauda epididymis. This treatment also altered the sperm transit time in epididymis, epididymal sperm reserves, sperm lipid peroxidation, and antioxidant enzymes activity. The results suggest that clonidine was able to affect the sperm quantity and quality by decreasing the transit time related to the increase in the frequency and amplitude of spontaneous contractions in epididymis, although the contractions induced by adrenergic agonists were desensitized.
α2肾上腺素能受体的选择性激动剂可乐定的使用与生育能力受损有关。因此，已有描述表明附睾功能的改变与生育能力丧失有关。因此，本研究旨在进一步评估可乐定对大鼠附睾尾远端收缩的影响及其对精子参数的影响。通过药理学实验评估可乐定对离体附睾尾远端的体外作用。可乐定在附睾尾远端的连续收缩反应表现出脱敏现象。体外可乐定预处理（10(-5)M，10分钟）后，去甲肾上腺素诱导的收缩反应出现脱敏。如果在咪唑克生（α2肾上腺素能受体拮抗剂）存在的情况下进行体外预处理，可乐定就无法改变去甲肾上腺素的收缩反应，而哌唑嗪（α1肾上腺素能受体拮抗剂）则无效。此外，体外可乐定预处理增加了附睾尾远端自发收缩的频率和幅度。另外，为了诱导α2肾上腺素能受体的体内脱敏，给雄性Wistar大鼠用递增剂量的可乐定进行处理，并分析附睾尾远端的收缩情况和精子参数。可乐定的体内处理降低了肾上腺素能激动剂诱导的收缩效力，并增加了附睾尾远端自发收缩的频率和幅度。这种处理还改变了精子在附睾中的转运时间、附睾精子储备、精子脂质过氧化和抗氧化酶活性。结果表明，可乐定能够通过缩短与附睾自发收缩频率和幅度增加相关的转运时间来影响精子数量和质量，尽管肾上腺素能激动剂诱导的收缩反应出现了脱敏。
