Endothelium-dependent hyperpolarization-mediated vasodilatation compensates nitric oxide-mediated endothelial dysfunction during ischemia in diabetes-induced canine coronary collateral microcirculation in vivo

Toyotaka Yada, Hiroaki Shimokawa, Hiroyuki Tachibana

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Objectives: It has been previously demonstrated that endothelial caveolin-1 plays crucial roles to produce an endothelium-derived hyperpolarizing factor in mouse mesenteric arteries. We examined whether this mechanism is involved in the endothelium-dependent hyperpolarization-mediated responses to compensate reduced NO-mediated responses in diabetes mellitus during coronary occlusion in dogs in vivo. Methods: Canine subepicardial collateral coronary small arteries (≥100 μm) and arterioles (<100 μm) were observed by an intravital microscope. Experiments were performed during occlusion of the left anterior descending coronary artery (90 minutes) under the following conditions (n = 6 each); (i) control, (ii) diabetes mellitus, and (iii) diabetes mellitus+L-NMMA+KC a channel blockade. Vascular and myocardial levels of caveolin-1, eNOS, and caspase-3 were measured by ELISA. Results: Caveolin-1 levels in the ischemic area were greater in coronary microvessels than in conduit arteries in the control group. NO-mediated coronary vasodilatations of small arteries to bradykinin did not increase in diabetes mellitus associated with decreased eNOS phosphorylation at Ser1177 compared with baseline of controls and were restored by compensation of endothelium-dependent hyperpolarization and were suppressed by KC a channel blockade. Conclusions: NO-mediated vasodilatations of small coronary arteries during coronary occlusion are impaired in diabetes mellitus and are compensated by endothelium-dependent hyperpolarization of arterioles in dogs in vivo.

Original languageEnglish
Article numbere12456
JournalMicrocirculation
Volume25
Issue number5
DOIs
Publication statusPublished - 2018 Jul

Keywords

  • caveolin-1
  • coronary
  • diabetes mellitus
  • endothelium-dependent hyperpolarization
  • microcirculation

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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