Varadharaj Saradhadevi, Porter Kyle, Pleister Adam, Wannemacher Jacob, Sow Angela, Jarjoura David, Zweier Jay L, Khayat Rami N
The Sleep Heart Program, the Ohio State University, Columbus, OH, United States; Division of Pulmonary Critical Care and Sleep, The Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, the Ohio State University, Columbus, OH, United States.
The Center for Biostatistics, the Ohio State University, Columbus, OH, United States.
Respir Physiol Neurobiol. 2015 Feb 1;207:40-7. doi: 10.1016/j.resp.2014.12.012. Epub 2014 Dec 19.
The mechanism of vascular endothelial dysfunction (VED) and cardiovascular disease in obstructive sleep apnea (OSA) is unknown. We performed a comprehensive evaluation of endothelial nitric oxide synthase (eNOS) function directly in the microcirculatory endothelial tissue of OSA patients who have very low cardiovascular risk status. Nineteen OSA patients underwent gluteal biopsies before, and after effective treatment of OSA. We measured superoxide (O2(•-)) and nitric oxide (NO) in the microcirculatory endothelium using confocal microscopy. We evaluated the effect of the NOS inhibitor l-Nitroarginine-Methyl-Ester (l-NAME) and the NOS cofactor tetrahydrobiopterin (BH4) on endothelial O2(•-) and NO in patient endothelial tissue before and after treatment. We found that eNOS is dysfunctional in OSA patients pre-treatment, and is a source of endothelial O2(•-) overproduction. eNOS dysfunction was reversible with the addition of BH4. These findings provide a new mechanism of endothelial dysfunction in OSA patients and a potentially targetable pathway for treatment of cardiovascular risk in OSA.
阻塞性睡眠呼吸暂停（OSA）中血管内皮功能障碍（VED）和心血管疾病的机制尚不清楚。我们直接在心血管风险极低的OSA患者的微循环内皮组织中对内皮型一氧化氮合酶（eNOS）功能进行了全面评估。19例OSA患者在OSA有效治疗前后接受了臀肌活检。我们使用共聚焦显微镜测量了微循环内皮中的超氧化物（O2(•-)）和一氧化氮（NO）。我们评估了一氧化氮合酶抑制剂L-硝基精氨酸甲酯（L-NAME）和一氧化氮合酶辅因子四氢生物蝶呤（BH4）对治疗前后患者内皮组织中内皮O2(•-)和NO的影响。我们发现，治疗前OSA患者的eNOS功能失调，是内皮O2(•-)过度产生的来源。添加BH4后，eNOS功能障碍是可逆的。这些发现为OSA患者内皮功能障碍提供了一种新机制，以及一条治疗OSA心血管风险的潜在可靶向途径。
