Kim Y C, Kim J H, Davies M G, Hagen P O, Carson C C
Sexual Dysfunction Laboratory, Duke University Medical Center, Durham, North Carolina.
J Urol. 1995 Mar;153(3 Pt 1):807-10.
The polypeptide VIP has been proposed as an inhibitory nonadrenergic, noncholinergic (NANC) neurotransmitter involved in the relaxation of cavernosal smooth muscle during erection. However, the specific mechanism(s) by which VIP exerts its effect is unknown. To determine whether VIP is involved in NANC-mediated cavernosal relaxation, strips of corpus cavernosum from New Zealand White rabbits were hung in tissue baths; atropine and guanethidine were added to block cholinergic and adrenergic neurotransmission, respectively. The tissue was then submaximally precontracted with norepinephrine (NE) and relaxed by electrical field stimulation (EFS; 10 V square waves, 0.5 msec. duration, 10 second trains at 5, 15 and 40 Hz) before and after preincubation with the VIP antagonist, VIP 10-28. To evaluate the role of nitric oxide (NO) and prostaglandins on the relaxant effect of VIP in the corpus cavernosum, the strips were contracted with NE and subsequently relaxed with cumulative doses of VIP (10(-10) to 10(-6) M.). After VIP dose-response curves were obtained, the strips were preincubated with N omega-nitro-L-arginine (NOARG, an inhibitor of nitric oxide synthase, 10(-4) M.) and the VIP dose-response curve was repeated. Indomethacin (10(-5) M.) was added to one-half of the NOARG treated strips to inhibit prostaglandin synthesis. VIP 10-28 inhibited EFS-induced relaxation (p < 0.05) and produced dose-dependent relaxation, which was inhibited by NOARG (p < 0.05). In contrast, the VIP-induced relaxation was more pronounced in the presence of indomethacin (p < 0.05). Moreover, indomethacin substantially reversed the NOARG inhibition of VIP relaxation (p < 0.05). These results suggest that VIP is a mediator of NANC cavernosal relaxation and that NO synthesis is involved in VIP-induced NANC relaxation in the corpus cavernosum. In addition, the presence of vasoconstrictive prostanoids modulates this VIP-mediated NANC relaxation. Therefore, VIP appears to contribute to NANC neurally mediated cavernosal relaxation, and its mechanisms of relaxation are dependent on prostanoid and involve the generation of NO.
多肽血管活性肠肽（VIP）被认为是一种抑制性非肾上腺素能、非胆碱能（NANC）神经递质，参与勃起过程中海绵体平滑肌的舒张。然而，VIP发挥作用的具体机制尚不清楚。为了确定VIP是否参与NANC介导的海绵体舒张，将新西兰白兔的海绵体条悬挂于组织浴槽中；分别加入阿托品和胍乙啶以阻断胆碱能和肾上腺素能神经传递。然后用去甲肾上腺素（NE）使组织产生亚最大预收缩，并在与VIP拮抗剂VIP 10 - 28预孵育前后，通过电场刺激（EFS；10V方波，持续时间0.5毫秒，5、15和40Hz频率下刺激10秒）使其舒张。为了评估一氧化氮（NO）和前列腺素在VIP对海绵体舒张作用中的作用，将海绵体条用NE收缩，随后用累积剂量的VIP（10⁻¹⁰至10⁻⁶M）使其舒张。获得VIP剂量反应曲线后，将海绵体条用Nω-硝基-L-精氨酸（NOARG，一氧化氮合酶抑制剂，10⁻⁴M）预孵育，然后重复VIP剂量反应曲线。将吲哚美辛（10⁻⁵M）加入一半经NOARG处理的海绵体条中以抑制前列腺素合成。VIP 10 - 28抑制EFS诱导的舒张（p < 0.05）并产生剂量依赖性舒张，而这被NOARG抑制（p < 0.05）。相反，在吲哚美辛存在的情况下，VIP诱导的舒张更明显（p < 0.05）。此外，吲哚美辛显著逆转了NOARG对VIP舒张的抑制作用（p < 0.05）。这些结果表明，VIP是NANC介导的海绵体舒张的介质，并且NO的合成参与了VIP诱导的海绵体NANC舒张。此外，缩血管前列腺素的存在调节这种VIP介导的NANC舒张。因此，VIP似乎有助于NANC神经介导的海绵体舒张，其舒张机制依赖于前列腺素并涉及NO的生成。
