The effects of the combined use of a PDE5 inhibitor and medications for hypertension, lower urinary tract symptoms and dyslipidemia on corporal tissue tone
The effects of the combined use of a PDE5 inhibitor and medications for hypertension, lower urinary tract symptoms and dyslipidemia on corporal tissue tone
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PDE5抑制剂与高血压、下尿路症状和血脂异常药物联合使用对体组织张力的影响
DOI：
10.1038/ijir.2012.19
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发表时间：
2012
影响因子：
2.6
通讯作者：
SW Lee
中科院分区：
文献类型：
--
作者：
JH Lee;MR Chae;JK Park;JH Jeon;SW Lee
艾德与其合并症（高血压、血脂异常和下尿路症状（LUTS））密切相关。因此，有几种药物与PDE 5抑制剂同时使用。如果治疗艾德合并症的特定药物对PDE 5抑制剂具有增强作用，则它为对PDE 5抑制剂单药治疗无反应的患者提供替代联合治疗，并允许临床医生同时治疗艾德及其合并症。为给艾德及其伴随疾病选择合适的药物提供理论依据，我们采用器官浴技术，检测了PDE 5抑制剂与高血压、血脂异常和LUTS代表性药物联合使用对家兔阴茎海绵体的舒张作用。10−4 M氯沙坦、10 −6 M硝苯地平、10 − 6 M硝苯地平、10−7 M多沙唑嗪和10−9 M坦索罗辛可显著增强米罗地那非对苯肾上腺素诱导的海绵体收缩的舒张作用（P<0.05）。最大舒张效应分别为47.2± 3.8%、57.6± 2.6%、64.0± 3.7%、76.1±5.7%和71.7± 5.4%。依那普利和辛伐他汀无增强作用。单独硝普钠引起的舒张（39.0±4.0%）在10−4 M氯沙坦存在下显著增强（66.0± 6.0%，P<0.05）。四乙基铵（1 mM）显著抑制坦索罗辛和多沙唑嗪对米罗那非诱导的舒张的增强作用（多沙唑嗪：76.1±5.7% vs 45.3±2.3%;坦索罗辛：71.7±5.4% vs 48.1±3.5%）。在这些发现的基础上，氯沙坦似乎通过与一氧化氮的相互作用诱导协同效应。此外，K+通道激活可能是米罗地那非与多沙唑嗪或坦索罗辛联合使用的协同作用机制之一。我们认为，联合使用PDE 5抑制剂与氯沙坦、硝苯地平、曲马多、多沙唑嗪或坦索罗辛可能是同时治疗艾德及其合并症和增加对PDE 5抑制剂应答率的药理学策略。
ED is closely associated with its comorbidities (hypertension, dyslipidemia and lower urinary tract symptoms (LUTS)). Therefore, several drugs have been prescribed simultaneously with PDE5 inhibitors. If a specific medication for ED comorbidities has enhancing effects on PDE5 inhibitors, it offers alternative combination therapy in nonresponders to monotherapy with PDE5 inhibitors and allows clinicians to treat ED and its comorbidities simultaneously. To establish theoretical basis of choosing an appropriate medication for ED and concomitant disease, we examined the effects combining a PDE5 inhibitor with representative drugs for hypertension, dyslipidemia and LUTS on relaxing the corpus cavernosum of rabbits using the organ-bath technique. The effect of mirodenafil on relaxing phenylephrine-induced cavernosal contractions was significantly enhanced by the presence of 10−4 M losartan, 10−6 M nifedipine, 10−6 M amlodipine, 10−7 M doxazosin and 10−9 M tamsulosin (P<0.05). The maximum relaxation effects were 47.2±3.8%, 57.6±2.6%, 64.0±3.7%, 76.1±5.7% and 71.7±5.4%, respectively. Enalapril and simvastatin had no enhancing effects. The relaxation induced by sodium nitroprusside alone (39.0±4.0%) was significantly enhanced in the presence of the 10−4 M losartan (66.0±6.0%, P<0.05). Tetraethylammonium (1 mM) significantly inhibited the enhancement effects of tamsulosin and doxazosin on mirodenafil-induced relaxation (doxazosin: 76.1±5.7% vs 45.3±2.3%; tamsulosin: 71.7±5.4% vs 48.1±3.5%). On the basis of these findings, losartan seemed to induce synergistic effects through an interaction with nitric oxide. In addition, K+ channel activation could be one of the mechanisms for the synergistic effect of combining mirodenafil with doxazosin or tamsulosin. We believe that the combination of a PDE5 inhibitor with losartan, nifedipine, amlodipine, doxazosin or tamsulosin could be a pharmacologic strategy for simultaneously treating ED and its comorbidities and increasing response rates to PDE5 inhibitors.
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影响因子：
20.1
作者：
Kifor,I;Dzau,VJ
通讯作者：
Dzau,VJ
DOI：
10.1152/ajpgi.00034.2010
发表时间：
2010-06-01
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.91.3.1044
发表时间：
1994-02-01
影响因子：
11.1
作者：
WHITE, CR;BROCK, TA;TARPEY, MM
通讯作者：
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