Ghasemi Mehdi, Sadeghipour Hamed, Dehpour Ahmad R
Department of Pharmacology, School of Medicine, Medical Sciences/University of Tehran, PO Box 13145-784, Tehran, Iran.
BJU Int. 2007 Dec;100(6):1385-90. doi: 10.1111/j.1464-410X.2007.07180.x. Epub 2007 Sep 10.
To investigate the ability of acute administration of the endogenous cannabinoid, anandamide, in vitro to alter the nonadrenegic noncholinergic (NANC)-mediated relaxation of corpus cavernosum (CC) in diabetic rats and the possible role of nitric oxide (NO), as it is well known that erectile dysfunction (ED) affects 35-75% of men with diabetes mellitus and several studies have been conducted to find appropriate strategies for treating diabetes-induced ED.
Diabetes was induced in rats by streptozotocin administration and was maintained for 8 weeks. The CC were removed and isolated in organ baths for pharmacological studies. Agonist-evoked or electrical-field stimulation (EFS)-evoked smooth muscle tensions in CC strips from control and diabetic rats were measured.
The neurogenic relaxation of phenylephrine (7.5 microm)-precontracted isolated CC strips was impaired in diabetic rats. Anandamide (0.3, 1 and 3 microm) enhanced the relaxant responses to EFS in diabetic CC strips in a dose-dependent manner. This effect was antagonized by the selective cannabinoid CB(1) receptor antagonist AM251 (1 microm) and the selective vanilloid receptor antagonist capsazepine (3 microm). Concurrent administration of partially effective doses of l-arginine (10 microm) and anandamide (0.3 microm) exerted a synergistic improvement in EFS-induced relaxation of diabetic CC strips (P < 0.001). The relaxant responses to the NO donor, sodium nitroprusside, were similar between diabetic and control groups. CONCLUSION; For the first time, we show that acute administration of anandamide, an endogenous cannabinoid, alone or combined with l-arginine can improve nitrergic nerve-mediated relaxation of the CC in diabetic rats. This effect was mediated by cannabinoid CB(1) and vanilloid VR(1) receptors within the CC.
研究内源性大麻素花生四烯乙醇胺急性给药在体外对糖尿病大鼠阴茎海绵体（CC）非肾上腺素能非胆碱能（NANC）介导的舒张功能的影响，以及一氧化氮（NO）的可能作用。众所周知，勃起功能障碍（ED）影响35%-75%的糖尿病男性患者，并且已经开展了多项研究来寻找治疗糖尿病性ED的合适策略。
通过给予链脲佐菌素诱导大鼠患糖尿病，并维持8周。取出CC并分离于器官浴槽中进行药理学研究。测量对照和糖尿病大鼠CC条中激动剂诱发或电场刺激（EFS）诱发的平滑肌张力。
糖尿病大鼠中，去氧肾上腺素（7.5微摩尔）预收缩的离体CC条的神经源性舒张功能受损。花生四烯乙醇胺（0.3、1和3微摩尔）以剂量依赖的方式增强糖尿病CC条对EFS的舒张反应。该作用被选择性大麻素CB(1)受体拮抗剂AM251（1微摩尔）和选择性香草酸受体拮抗剂辣椒素（3微摩尔）拮抗。同时给予部分有效剂量的L-精氨酸（10微摩尔）和花生四烯乙醇胺（0.3微摩尔）对糖尿病CC条EFS诱导的舒张产生协同改善作用（P<0.001）。糖尿病组和对照组对NO供体硝普钠的舒张反应相似。结论：我们首次表明，内源性大麻素花生四烯乙醇胺单独或与L-精氨酸联合急性给药可改善糖尿病大鼠CC中一氧化氮能神经介导的舒张功能。该作用由CC内的大麻素CB(1)和香草酸VR(1)受体介导。
