Ahn T Y, Gómez-Coronado D, Martínez V, Cuevas P, Goldstein I, Sáenz de Tejada I
Department of Urology, Boston University School of Medicine, Massachusetts, USA.
Int J Impot Res. 1999 Feb;11(1):9-14. doi: 10.1038/sj.ijir.3900378.
We have investigated the effect of oxidatively-modified low density lipoproteins (ox-LDL) on the contractility of rabbit trabecular smooth muscle. Low density lipoproteins (LDL) were isolated from fresh human plasma pooled from multiple donors and oxidized by exposure to copper. Corpus cavernosum strips from New Zealand White rabbits were studied in organ chambers for isometric tension measurement. Corporeal strips in which moderate tone was induced by phenylephrine, contracted when exposed to ox-LDL, but not when exposed to either native LDL (nLDL) or LDL protected from oxidation by butylated hydroxytoleune (BHT-LDL). Removal of the endothelium, or treatment of the corporeal strips with N(omega)-nitro-L-arginine (nitric oxide synthase inhibitor), methylene blue of LY83583 (guanylate cyclase inhibitors/superoxide producing agents), did not prevent ox-LDL-induced contraction. ox-LDL, dose-dependently, enhanced the contractile response of corporeal strips to low and moderate concentrations by phenylephrine. nLDL had no significant effect on phenylephrine-induced contraction of corporeal strips. ox-LDL, nLDL or BHT-LDL had no effect on relaxation induced by the endothelium-dependent dilator, acetylcholine, or the nitric oxide donor, nitroprusside. In conclusion, this present study demonstrates significant pro-contractile effects of ox-LDL on corporeal smooth muscle, this effect is independent of the endothelium or the nitric oxide/cGMP pathway. The pro-contractile effect of ox-LDL may interfere with penile smooth muscle relaxation, necessary for the initiation and maintenance of penile erection.
我们研究了氧化修饰的低密度脂蛋白(ox-LDL)对兔小梁平滑肌收缩性的影响。从多个供体汇集的新鲜人血浆中分离出低密度脂蛋白(LDL),并通过暴露于铜进行氧化。在器官浴槽中研究新西兰白兔阴茎海绵体条带的等长张力测量。用去氧肾上腺素诱导适度张力的阴茎海绵体条带,在暴露于ox-LDL时收缩,但暴露于天然LDL(nLDL)或经丁基化羟基甲苯(BHT-LDL)保护而未被氧化的LDL时不收缩。去除内皮,或用N(ω)-硝基-L-精氨酸(一氧化氮合酶抑制剂)、亚甲蓝或LY83583(鸟苷酸环化酶抑制剂/超氧化物产生剂)处理阴茎海绵体条带,均不能阻止ox-LDL诱导的收缩。ox-LDL剂量依赖性地增强阴茎海绵体条带对低浓度和中等浓度去氧肾上腺素的收缩反应。nLDL对去氧肾上腺素诱导的阴茎海绵体条带收缩无显著影响。ox-LDL、nLDL或BHT-LDL对内皮依赖性舒张剂乙酰胆碱或一氧化氮供体硝普钠诱导的舒张无影响。总之,本研究表明ox-LDL对阴茎海绵体平滑肌具有显著的促收缩作用,这种作用独立于内皮或一氧化氮/cGMP途径。ox-LDL的促收缩作用可能会干扰阴茎勃起启动和维持所必需的阴茎平滑肌舒张。