Azadzoi K M, Saenz de Tejada I
Department of Urology, Boston University Medical Center, Massachusetts.
J Urol. 1991 Jul;146(1):238-40. doi: 10.1016/s0022-5347(17)37759-5.
The majority of cases of impotence are associated with vascular risk factors such as diabetes, hypercholesterolemia, hypertension and smoking. These factors induce impairment of endothelium-dependent relaxation of blood vessels in man and in experimental animals. In this study the effects of hypercholesterolemia on the reactivity of rabbit corpus cavernosum smooth muscle strips to endothelium-dependent and endothelium-independent agents were investigated. New Zealand White rabbits (n = 14) were randomly divided into control and treatment groups. The control group (n = 7) received a regular diet while the treatment group (n = 7) was fed a diet of 0.5% cholesterol and 4% peanut oil for 10 weeks. Animals were then sacrificed and the corporal tissue studied in organ chambers for isometric tension measurement. Tissue was contracted with phenylephrine and concentration-dependent relaxation to acetylcholine, in the presence and absence of indomethacin, and to nitroprusside were examined. Blood level of cholesterol in the cholesterol-fed group was significantly higher compared to the control group. Contractions to phenylephrine were similar in both groups. Hypercholesterolemia, however, inhibited relaxation to acetylcholine but did not alter relaxation to nitroprusside, a cyclic guanosine monophosphate (cGMP)-dependent, direct smooth muscle dilator. Indomethacin enhanced the relaxations to acetylcholine in both control and cholesterol-fed groups but did not correct the difference in the relaxation to acetylcholine between both groups. It is concluded that hypercholesterolemia impairs endothelium-mediated relaxation of rabbit corpus cavernosum smooth muscle. The mechanism for the endothelial dysfunction does not appear to involve alteration in cyclooxygenase products of arachidonate or the cGMP-dependent relaxation of corporal smooth muscle. Impairment of endothelium-dependent relaxation of corporal smooth muscle may contribute to the pathophysiology of impotence associated with hypercholesterolemia in man.
大多数阳痿病例与血管危险因素有关，如糖尿病、高胆固醇血症、高血压和吸烟。这些因素在人和实验动物中都会导致血管内皮依赖性舒张功能受损。在本研究中，研究了高胆固醇血症对兔海绵体平滑肌条对内皮依赖性和非内皮依赖性药物反应性的影响。将14只新西兰白兔随机分为对照组和治疗组。对照组（n = 7）给予常规饮食，而治疗组（n = 7）喂食含0.5%胆固醇和4%花生油的饮食10周。然后处死动物，在器官浴槽中研究海绵体组织以进行等长张力测量。用去氧肾上腺素使组织收缩，并在有和没有吲哚美辛的情况下，检测对乙酰胆碱和硝普钠的浓度依赖性舒张反应。喂食胆固醇组的血液胆固醇水平明显高于对照组。两组对去氧肾上腺素的收缩反应相似。然而，高胆固醇血症抑制了对乙酰胆碱的舒张反应，但不改变对硝普钠（一种环磷酸鸟苷（cGMP）依赖性的直接平滑肌舒张剂）的舒张反应。吲哚美辛增强了对照组和喂食胆固醇组对乙酰胆碱的舒张反应，但未纠正两组之间对乙酰胆碱舒张反应的差异。得出的结论是，高胆固醇血症损害兔海绵体平滑肌的内皮介导舒张功能。内皮功能障碍的机制似乎不涉及花生四烯酸环氧化酶产物的改变或海绵体平滑肌的cGMP依赖性舒张。海绵体平滑肌内皮依赖性舒张功能受损可能有助于人类与高胆固醇血症相关的阳痿的病理生理学。
