Ari G, Vardi Y, Finberg J P
Pharmacology Unit, Rappaport Family Faculty of Medicine, Technion, POB 9649, Haifa 31096, Israel.
Clin Sci (Lond). 1999 Apr;96(4):365-71.
The purpose of this investigation was to study the time course, response to insulin and characteristics of erectile dysfunction in streptozotocin (STZ)-diabetic Sprague-Dawley rats, and the function of the NO-generating system in these animals. Copulation-induced and reflex erection were quantified in conscious Sprague-Dawley rats at different times after injection of STZ. The corporal vasodilatation response to nerve stimulation was studied by measuring the rise in corporal pressure in pithed rats following electrical stimulation of sacral spinal nerve roots. The activity of NO synthase was determined in corporal tissue by measuring the generation of [3H]citrulline from [3H]arginine. Copulation-induced erection was inhibited at 1 and 2 months after STZ treatment, but this could be prevented by a short (2-week) pretreatment with insulin. Reflex erection was inhibited at 1, 4, 6 and 9 months after STZ; at 6 months, this inhibition was also reversible by insulin pretreatment. Following pithing, the basal corporal pressure was elevated in diabetic rats. At 4 months after STZ, this increase was normalized by a 2-week, but not by a 1-week, pretreatment with insulin; however, at 9 months after STZ, insulin pretreatment did not normalize corporal pressure. The increase in corporal pressure caused by stimulation of sacral nerve roots in pithed rats was enhanced in diabetic animals. This enhancement was also normalized at 4 months, but not at 9 months, by 2 weeks of insulin treatment. The inhibition of the stimulation-induced increase in corporal pressure by NG-nitro-L-arginine methyl ester (5 mg/kg) was less following 9 months of diabetes, although NO synthase activity was normal in cavernosal tissue following 6-8 months of diabetes. In conclusion, STZ-induced diabetes caused changes in the erectile system that were initially reversible by a short insulin treatment, but which with time (more than 6 months) became irreversible. NO synthase activity in cavernosal tissue was normal, but the response to NG-nitro-L-arginine methyl ester was inhibited in long-term diabetes (9 months).
本研究旨在探讨链脲佐菌素（STZ）诱导的糖尿病Sprague-Dawley大鼠勃起功能障碍的时间进程、对胰岛素的反应及特征，以及这些动物体内一氧化氮生成系统的功能。在注射STZ后的不同时间，对清醒的Sprague-Dawley大鼠的交配诱导勃起和反射性勃起进行量化。通过测量去脑大鼠在电刺激骶神经根后海绵体内压力的升高，研究海绵体对神经刺激的血管舒张反应。通过测量从[3H]精氨酸生成[3H]瓜氨酸的量，测定海绵体组织中一氧化氮合酶的活性。STZ治疗后1个月和2个月，交配诱导勃起受到抑制，但短期（2周）胰岛素预处理可预防这种情况。STZ治疗后1、4、6和9个月，反射性勃起受到抑制；在6个月时，胰岛素预处理也可使这种抑制作用逆转。去脑后，糖尿病大鼠的海绵体基础压力升高。STZ治疗后4个月，2周的胰岛素预处理可使这种升高恢复正常，但1周的预处理则不能；然而，STZ治疗后9个月，胰岛素预处理未能使海绵体压力恢复正常。糖尿病动物中，去脑大鼠刺激骶神经根引起的海绵体内压力升高增强。胰岛素治疗2周后，这种增强在4个月时恢复正常，但在9个月时未恢复正常。糖尿病9个月后，NG-硝基-L-精氨酸甲酯（5 mg/kg）对刺激诱导的海绵体内压力升高的抑制作用减弱，尽管糖尿病6-8个月后海绵体组织中的一氧化氮合酶活性正常。总之，STZ诱导的糖尿病导致勃起系统发生变化，最初短期胰岛素治疗可使其逆转，但随着时间推移（超过6个月）变得不可逆。海绵体组织中的一氧化氮合酶活性正常，但长期糖尿病（9个月）时对NG-硝基-L-精氨酸甲酯的反应受到抑制。
