eNOS-uncoupling in age-related erectile dysfunction.
eNOS-uncoupling in age-related erectile dysfunction.
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DOI：
10.1038/ijir.2011.2
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发表时间：
2011-03
影响因子：
2.6
通讯作者：
Musicki, B.
中科院分区：
文献类型：
--
作者：
Johnson, J. M.;Bivalacqua, T. J.;Lagoda, G. A.;Burnett, A. L.;Musicki, B.
衰老与ED有关。尽管年龄相关的艾德主要归因于阴茎中氧化应激和内皮功能障碍的增加，但这种效应的分子机制尚未完全确定。我们评估是否内皮型一氧化氮合酶（eNOS）解偶联在老年大鼠阴茎是一个贡献机制。与此相关，我们评估了用eNOS辅因子四氢生物蝶呤（BH 4）替代对老年大鼠勃起功能的影响。雄性Fischer 344“年轻”（4月龄）和“年老”（19月龄）大鼠用BH 4前体sepiapterin（10 mg/kg腹腔内）或溶媒处理4天。1天洗脱后，评估勃起功能对海绵体神经电刺激的反应。内皮功能障碍（eNOS解偶联）和氧化应激（硫代巴比妥酸反应物质，TBARS）进行蛋白质印迹法测定阴茎样品。勃起反应显着降低，而eNOS解偶联和TBARS生产显着增加，在老年大鼠阴茎与年轻大鼠相比。Sepiapterin显着改善老年大鼠的勃起反应，并防止增加TBARS生产，但不影响eNOS解偶联在老年大鼠的阴茎。这些发现表明，衰老诱导阴茎中的eNOS解偶联，导致氧化应激和ED增加。
Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH4) on erectile function in the aged rats. Male Fischer 344 ‘young’ (4-month-old) and ‘aged’ (19-month-old) rats were treated with a BH4 precursor sepiapterin (10 mg/kg intraperitoneally) or vehicle for 4 days. After 1-day washout, erectile function was assessed in response to electrical stimulation of the cavernous nerve. Endothelial dysfunction (eNOS uncoupling) and oxidative stress (thiobarbituric acid reactive substances, TBARS) were measured by conducting western blot in penes samples. Erectile response was significantly reduced in aged rats, whereas eNOS uncoupling and TBARS production were significantly increased in the aged rat penis compared with young rats. Sepiapterin significantly improved erectile response in aged rats and prevented increase in TBARS production, but did not affect eNOS uncoupling in the penis of aged rats. These findings suggest that aging induces eNOS uncoupling in the penis, resulting in increased oxidative stress and ED.
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DOI：
10.1152/ajpheart.00770.2002
发表时间：
2003-04-01
影响因子：
4.8
作者：
Bivalacqua, TJ;Armstrong, JS;Champion, HC
通讯作者：
Champion, HC
影响因子：
10.8
作者：
Ferrini, MG;Davila, HH;Rajfer, J
通讯作者：
Rajfer, J
影响因子：
6.6
作者：
Carrier, S;Nagaraju, P;Lue, TF
通讯作者：
Lue, TF
DOI：
10.1073/pnas.052712499
发表时间：
2002-03-19
影响因子：
11.1
作者：
Hurt, KJ;Musicki, B;Burnett, AL
通讯作者：
Burnett, AL
影响因子：
3.5
作者：
Hannan, Johanna L.;Blaser, Mark C.;Adams, Michael A.
通讯作者：
Adams, Michael A.