Tetrahydrobiopterin Restores Microvascular Dysfunction in Young Adult Binge Drinkers.
Tetrahydrobiopterin Restores Microvascular Dysfunction in Young Adult Binge Drinkers.
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DOI：
10.1111/acer.14254
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发表时间：
2020-02
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影响因子：
--
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反复狂饮与微血管功能下降有关。然而，微血管对病理生理刺激（如高压）的反应以及暴饮暴食诱导的微血管功能障碍的潜在机制尚不清楚。因此，使用离体实验模型，我们检测了有反复酗酒史的年轻人在短暂的高腔内压后孤立小动脉的微血管反应。此外，我们还研究了内皮一氧化氮合酶辅助因子四氢生物蝶呤的应用是否会恢复年轻酗酒者对血流和高腔内压的微血管功能。从年轻成年酗酒者（BD, n=14）、中度饮酒者（MODs, n=10）和戒酒者（ABs, n=12，平均年龄：23.7±0.5岁，体重指数：23.4±0.4 kg m - 2）中获得分离的皮下脂肪小动脉。应用四氢生物蝶呤和不应用四氢生物蝶呤检测急性高腔内压前后小动脉血流诱导扩张（FID，压力梯度：Δ10-100 cm H2O）。高压前，bp在Δ60和Δ100 cm H2O压力梯度下的FID分别比ABs低14%和18% (P<0.05)，而MODs和ABs在所有压力梯度下的FID相似（P≥0.2）。高压后，bd的FID进一步降低了10% (P<0.0005)，四氢生物蝶呤治疗可改善这种损害（提高4-26%，P<0.005）。而高压后MODs和ABs的FID无明显变化（P≥0.5）。急性病理生理刺激可加重年轻酗酒者微血管功能障碍。这些暴饮暴食引起的功能障碍可能被四氢生物蝶呤逆转，这表明氧化应激和/或非偶联内皮一氧化氮合酶在暴饮暴食中的作用。
Repeated binge drinking is associated with reduced microvascular function. However, microvascular responses to pathophysiological stimulus such as high pressure as well as potential mechanisms that underlie binge-induced microvascular dysfunction are unknown. Therefore, using an ex vivo experimental model, we examined microvascular responses following a brief period of high intraluminal pressure in isolated arterioles from young adults who have a history of repeated binge drinking. In addition, we examined if the application of the endothelial nitric oxide synthase cofactor, tetrahydrobiopterin, would restore microvascular function in response to flow and high intraluminal pressure in young adult binge drinkers. Isolated subcutaneous adipose arterioles were obtained from young adult binge drinkers (BD; n=14), moderate drinkers (MODs; n=10), and alcohol abstainers (ABs; n=12; mean age: 23.7±0.5 yrs and body mass index: 23.4±0.4 kg m−2). Arteriolar flow-induced dilation (FID, pressure gradient: Δ10-100 cm H2O) was measured before and after acute high intraluminal pressure with and without tetrahydrobiopterin. Before high pressure, FID at Δ60 and Δ100 cm H2O pressure gradient in BDs was 14% lower and 18% lower respectively than ABs (P<0.05), while MODs and ABs had similar FID across all pressure gradients (P≥0.2). After high pressure, FID in BDs was further reduced by 10% (P<0.0005) and this impairment was ameliorated by the treatment of tetrahydrobiopterin (4-26% higher, P<0.005). In contrast, FID after high pressure did not change in MODs and ABs (P≥0.5). Microvascular dysfunction in young adult binge drinkers may be exacerbated with acute pathophysiological stimulus. These binge-induced dysfunctions may be reversed by tetrahydrobiopterin, which suggests a role of oxidative stress and/or uncoupled endothelial nitric oxide synthase in binge drinking.
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DOI：
10.1111/acer.13565
发表时间：
2018-03
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Bian JT;Piano MR;Kotlo KU;Mahmoud AM;Phillips SA
通讯作者：
Phillips SA
影响因子：
5
作者：
Pletcher, MJ;Varosy, P;Hulley, SB
通讯作者：
Hulley, SB
DOI：
10.1152/ajpheart.00465.2002
发表时间：
2003-04-01
影响因子：
4.8
作者：
Bosnjak, JJ;Terata, K;Gutterman, DD
通讯作者：
Gutterman, DD
DOI：
10.1152/ajplung.00238.2016
发表时间：
2016-10-01
影响因子：
4.9
作者：
Dikalova, Anna;Aschner, Judy L.;Fike, Candice D.
通讯作者：
Fike, Candice D.
影响因子：
3.4
作者：
Gonzaga, Natalia A.;Callera, Glaucia E.;Tirapelli, Carlos R.
通讯作者：
Tirapelli, Carlos R.