title: 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.
  
  
  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.affiliation: From the Division of Cardiology, Pulmonology, and Vascular Medicine (D.S., R.S., A.R.-M., G.W., M.K., C.H.), Institute for Pharmacology and Clinical Pharmacology (T.F., J.W.F.), Central Institute of Clinical Chemistry and Laboratory Medicine (J.H.), and IUF-Leibniz Research Institute for Environmental Medicine (C.G., J.A., J.H.), University Duesseldorf, Medical Faculty, Duesseldorf, Germany; and Department of Nutrition, University of California, Davis (T.Y.M.).
authors.forename: Dominik
authors.initials: D
authors.lastname: Schuler
authors.affiliation: From the Division of Cardiology, Pulmonology, and Vascular Medicine (D.S., R.S., A.R.-M., G.W., M.K., C.H.), Institute for Pharmacology and Clinical Pharmacology (T.F., J.W.F.), Central Institute of Clinical Chemistry and Laboratory Medicine (J.H.), and IUF-Leibniz Research Institute for Environmental Medicine (C.G., J.A., J.H.), University Duesseldorf, Medical Faculty, Duesseldorf, Germany; and Department of Nutrition, University of California, Davis (T.Y.M.).
authors.forename: Roberto
authors.initials: R
authors.lastname: Sansone
authors.affiliation: From the Division of Cardiology, Pulmonology, and Vascular Medicine (D.S., R.S., A.R.-M., G.W., M.K., C.H.), Institute for Pharmacology and Clinical Pharmacology (T.F., J.W.F.), Central Institute of Clinical Chemistry and Laboratory Medicine (J.H.), and IUF-Leibniz Research Institute for Environmental Medicine (C.G., J.A., J.H.), University Duesseldorf, Medical Faculty, Duesseldorf, Germany; and Department of Nutrition, University of California, Davis (T.Y.M.).
authors.forename: Till
authors.initials: T
authors.lastname: Freudenberger
authors.affiliation: From the Division of Cardiology, Pulmonology, and Vascular Medicine (D.S., R.S., A.R.-M., G.W., M.K., C.H.), Institute for Pharmacology and Clinical Pharmacology (T.F., J.W.F.), Central Institute of Clinical Chemistry and Laboratory Medicine (J.H.), and IUF-Leibniz Research Institute for Environmental Medicine (C.G., J.A., J.H.), University Duesseldorf, Medical Faculty, Duesseldorf, Germany; and Department of Nutrition, University of California, Davis (T.Y.M.).
authors.forename: Ana
authors.initials: A
authors.lastname: Rodriguez-Mateos
authors.affiliation: From the Division of Cardiology, Pulmonology, and Vascular Medicine (D.S., R.S., A.R.-M., G.W., M.K., C.H.), Institute for Pharmacology and Clinical Pharmacology (T.F., J.W.F.), Central Institute of Clinical Chemistry and Laboratory Medicine (J.H.), and IUF-Leibniz Research Institute for Environmental Medicine (C.G., J.A., J.H.), University Duesseldorf, Medical Faculty, Duesseldorf, Germany; and Department of Nutrition, University of California, Davis (T.Y.M.).
authors.forename: Gesine
authors.initials: G
authors.lastname: Weber
authors.affiliation: From the Division of Cardiology, Pulmonology, and Vascular Medicine (D.S., R.S., A.R.-M., G.W., M.K., C.H.), Institute for Pharmacology and Clinical Pharmacology (T.F., J.W.F.), Central Institute of Clinical Chemistry and Laboratory Medicine (J.H.), and IUF-Leibniz Research Institute for Environmental Medicine (C.G., J.A., J.H.), University Duesseldorf, Medical Faculty, Duesseldorf, Germany; and Department of Nutrition, University of California, Davis (T.Y.M.).
authors.forename: Tony Y
authors.initials: TY
authors.lastname: Momma
authors.affiliation: From the Division of Cardiology, Pulmonology, and Vascular Medicine (D.S., R.S., A.R.-M., G.W., M.K., C.H.), Institute for Pharmacology and Clinical Pharmacology (T.F., J.W.F.), Central Institute of Clinical Chemistry and Laboratory Medicine (J.H.), and IUF-Leibniz Research Institute for Environmental Medicine (C.G., J.A., J.H.), University Duesseldorf, Medical Faculty, Duesseldorf, Germany; and Department of Nutrition, University of California, Davis (T.Y.M.).
authors.forename: Christine
authors.initials: C
authors.lastname: Goy
authors.affiliation: From the Division of Cardiology, Pulmonology, and Vascular Medicine (D.S., R.S., A.R.-M., G.W., M.K., C.H.), Institute for Pharmacology and Clinical Pharmacology (T.F., J.W.F.), Central Institute of Clinical Chemistry and Laboratory Medicine (J.H.), and IUF-Leibniz Research Institute for Environmental Medicine (C.G., J.A., J.H.), University Duesseldorf, Medical Faculty, Duesseldorf, Germany; and Department of Nutrition, University of California, Davis (T.Y.M.).
authors.forename: Joachim
authors.initials: J
authors.lastname: Altschmied
authors.affiliation: From the Division of Cardiology, Pulmonology, and Vascular Medicine (D.S., R.S., A.R.-M., G.W., M.K., C.H.), Institute for Pharmacology and Clinical Pharmacology (T.F., J.W.F.), Central Institute of Clinical Chemistry and Laboratory Medicine (J.H.), and IUF-Leibniz Research Institute for Environmental Medicine (C.G., J.A., J.H.), University Duesseldorf, Medical Faculty, Duesseldorf, Germany; and Department of Nutrition, University of California, Davis (T.Y.M.).
authors.forename: Judith
authors.initials: J
authors.lastname: Haendeler
authors.affiliation: From the Division of Cardiology, Pulmonology, and Vascular Medicine (D.S., R.S., A.R.-M., G.W., M.K., C.H.), Institute for Pharmacology and Clinical Pharmacology (T.F., J.W.F.), Central Institute of Clinical Chemistry and Laboratory Medicine (J.H.), and IUF-Leibniz Research Institute for Environmental Medicine (C.G., J.A., J.H.), University Duesseldorf, Medical Faculty, Duesseldorf, Germany; and Department of Nutrition, University of California, Davis (T.Y.M.).
authors.forename: Jens W
authors.initials: JW
authors.lastname: Fischer
authors.affiliation: From the Division of Cardiology, Pulmonology, and Vascular Medicine (D.S., R.S., A.R.-M., G.W., M.K., C.H.), Institute for Pharmacology and Clinical Pharmacology (T.F., J.W.F.), Central Institute of Clinical Chemistry and Laboratory Medicine (J.H.), and IUF-Leibniz Research Institute for Environmental Medicine (C.G., J.A., J.H.), University Duesseldorf, Medical Faculty, Duesseldorf, Germany; and Department of Nutrition, University of California, Davis (T.Y.M.).
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.affiliation: From the Division of Cardiology, Pulmonology, and Vascular Medicine (D.S., R.S., A.R.-M., G.W., M.K., C.H.), Institute for Pharmacology and Clinical Pharmacology (T.F., J.W.F.), Central Institute of Clinical Chemistry and Laboratory Medicine (J.H.), and IUF-Leibniz Research Institute for Environmental Medicine (C.G., J.A., J.H.), University Duesseldorf, Medical Faculty, Duesseldorf, Germany; and Department of Nutrition, University of California, Davis (T.Y.M.). christian.heiss@med.uni-duesseldorf.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000503:physiopathology; D001783:Blood Flow Velocity; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D006940:Hyperemia / Q000000981:diagnostic imaging / Q000503:physiopathology; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D001057:Apolipoproteins E; D004791:Enzyme Inhibitors; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D019331:NG-Nitroarginine Methyl Ester
keywords: Doppler duplex ultrasonography; aging; blood flow velocity; endothelial nitric oxide synthase; femoral artery; flavonoids; vasodilation