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

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.

• Authors: 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
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 34 Issue 12 Pg. 2651-7 (Dec 2014) ISSN: 1524-4636 [Electronic] United States
• PMID: 25341800 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 American Heart Association, Inc.

Chemical References

• Apolipoproteins E
• Enzyme Inhibitors
• Nitric Oxide Synthase Type III
• Nos3 protein, mouse
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Apolipoproteins E (deficiency, genetics)
• Atherosclerosis (physiopathology)
• Blood Flow Velocity
• Disease Models, Animal
• Endothelium, Vascular (physiopathology)
• Enzyme Inhibitors (pharmacology)
• Femoral Artery (diagnostic imaging, physiopathology)
• Hindlimb (blood supply)
• Humans
• Hyperemia (diagnostic imaging, physiopathology)
• Ischemia (physiopathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide Synthase Type III (antagonists & inhibitors, metabolism)
• Phosphorylation
• Ultrasonography
• Vasodilation (drug effects, physiology)