Marked Impairment of Endothelium-Dependent Digital Vasodilatations in Patients with Microvascular Angina: Evidence for Systemic Small Artery Disease

Shoko Ohura-Kajitani, Takashi Shiroto, Shigeo Godo, Yosuke Ikumi, Akiyo Ito, Shuhei Tanaka, Koichi Sato, Jun Sugisawa, Satoshi Tsuchiya, Akira Suda, Tomohiko Shindo, Shohei Ikeda, Kiyotaka Hao, Yoku Kikuchi, Kotaro Nochioka, Yasuharu Matsumoto, Jun Takahashi, Satoshi Miyata, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Objective: 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 NG-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- A nd 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. Conclusions: These results provide the first evidence that both NO- A nd 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.

Original languageEnglish
Pages (from-to)1400-1412
Number of pages13
JournalArteriosclerosis, thrombosis, and vascular biology
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • arterioles
  • aspirin
  • biomarkers
  • humans
  • manometry

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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