Measurement of endothelium-dependent vasodilation in mice--brief report

Dominik Schuler, Roberto Sansone, Till Freudenberger, Ana Rodriguez-Mateos, Gesine Weber, Tony Y Momma, Christine Goy, Joachim Altschmied, Judith Haendeler, Jens W Fischer, Malte Kelm, Christian Heiss

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

OBJECTIVE: Endothelium-dependent, flow-mediated vasodilation after an increase in shear stress at the endothelial lining of conduit arteries during reactive hyperemia after ischemia is a fundamental principle of vascular physiology adapting blood flow to demand of supplied tissue. Flow-mediated vasodilation measurements have been performed in human studies and are of diagnostic and prognostic importance, but have been impossible because of technical limitations in transgenic mice to date, although these represent the most frequently used animal model in cardiovascular research.

APPROACH AND RESULTS: Using high-frequency ultrasound, we visualized, quantified, and characterized for the first time endothelium-dependent dilation of the femoral artery after temporal ischemia of the lower part of the hindlimb and demonstrated that the signaling was almost exclusively dependent on stimulation of endothelial nitric oxide synthase, similar to acetylcholine, completely abolished after pharmacological or genetic inhibition of endothelial nitric oxide synthase and endothelial denudation, substantially impaired in mice of increasing age and cholesterol-fed ApoE knock outs and increased by the dietary polyphenol (-)-epicatechin. Intra- and interindividual variability were similar to the human methodology.

CONCLUSIONS: The physiology of flow-mediated vasodilation in mice resembles that in humans underscoring the significance of this novel technology to noninvasively, serially, and reliably quantify flow-mediated vasodilation in transgenic mice.

Original languageEnglish
Pages (from-to)2651-7
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume34
Issue number12
DOIs
Publication statusPublished - Dec 2014

Keywords

  • Animals
  • Apolipoproteins E
  • Atherosclerosis
  • Blood Flow Velocity
  • Disease Models, Animal
  • Endothelium, Vascular
  • Enzyme Inhibitors
  • Femoral Artery
  • Hindlimb
  • Humans
  • Hyperemia
  • Ischemia
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide Synthase Type III
  • Phosphorylation
  • Ultrasonography
  • Vasodilation

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