From the Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Arterioscler Thromb Vasc Biol. 2020 May;40(5):1400-1412. doi: 10.1161/ATVBAHA.119.313704. Epub 2020 Apr 2.
It remains to be elucidated whether and how endothelial functions are impaired in peripheral circulation of patients with coronary functional disorders, such as vasospastic angina (VSA) and microvascular angina (MVA). We simultaneously examined endothelial functions of peripheral conduit and resistance arteries in patients with coronary functional disorders, with a special reference to NO and endothelium-dependent hyperpolarization factors. Approach and Results: Based on the results of invasive coronary acetylcholine testing and coronary physiological measurements, we divided 43 patients into 3 groups; VSA, MVA, and VSA+MVA. Endothelium-dependent vasodilatations of the brachial artery and fingertip arterioles to intra-arterial infusion of bradykinin were simultaneously evaluated by ultrasonography and peripheral arterial tonometry, respectively. To assess NO and endothelium-dependent hyperpolarization factors, measurements were repeated after oral aspirin and intra-arterial infusion of N-monomethyl-L-arginine. Additionally, endothelium-independent vasodilatations to sublingual nitroglycerin and plasma levels of biomarkers for endothelial functions were measured. Surprisingly, digital vasodilatations to bradykinin were almost absent in patients with MVA alone and those with VSA+MVA compared with those with VSA alone. Mechanistically, both NO- and endothelium-dependent hyperpolarization-mediated digital vasodilatations were markedly impaired in patients with MVA alone. In contrast, endothelium-independent vasodilatations to nitroglycerin were comparable among the 3 groups. Plasma levels of soluble VCAM (vascular cell adhesion molecule)-1 were significantly higher in patients with MVA alone compared with those with VSA alone.
These results provide the first evidence that both NO- and endothelium-dependent hyperpolarization-mediated digital vasodilatations are markedly impaired in MVA patients, suggesting that MVA is a cardiac manifestation of the systemic small artery disease.
目前尚不清楚伴有冠状动脉功能障碍（如血管痉挛性心绞痛[VSA]和微血管性心绞痛[MVA]）的患者外周循环中的内皮功能是否受损以及如何受损。我们同时检查了伴有冠状动脉功能障碍患者的外周输送和阻力动脉的内皮功能，并特别关注了一氧化氮[NO]和内皮依赖性超极化因子。
根据有创性冠状动脉乙酰胆碱检测和冠状动脉生理测量的结果，我们将 43 名患者分为 3 组：VSA 组、MVA 组和 VSA+MVA 组。通过超声和外周动脉张力计分别同时评估肱动脉和指尖小动脉对血管内缓激肽输注的内皮依赖性血管舒张作用。为了评估 NO 和内皮依赖性超极化因子，在口服阿司匹林和血管内输注 N-单甲基-L-精氨酸后重复测量。此外，还测量了舌下含服硝酸甘油的内皮非依赖性血管舒张作用和内皮功能的生物标志物的血浆水平。令人惊讶的是，与单独 VSA 组相比，单独 MVA 组和 VSA+MVA 组患者的指尖对缓激肽的血管舒张作用几乎消失。从机制上讲，单独 MVA 患者的 NO 和内皮依赖性超极化介导的指尖血管舒张作用明显受损。相比之下，3 组患者的硝酸甘油引起的内皮非依赖性血管舒张作用无差异。单独 MVA 组患者的可溶性血管细胞黏附分子-1[VCAM-1]的血浆水平明显高于单独 VSA 组。
这些结果首次提供了证据表明，单独 MVA 患者的 NO 和内皮依赖性超极化介导的指尖血管舒张作用明显受损，提示 MVA 是全身性小动脉疾病的心脏表现。
