In vivo measurement of flow-mediated vasodilation in living rats using high-resolution ultrasound

Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H1086-93. doi: 10.1152/ajpheart.00811.2007. Epub 2007 Nov 30.


In humans, endothelial vasodilator function serves as a surrogate marker for cardiovascular health and is measured as changes in conduit artery diameter after temporary ischemia [flow-mediated dilation (FMD)]. Here we present an FMD-related approach to study femoral artery (FA) vasodilation in anesthetized rats. Diameter and Doppler flow were monitored in the FA. Using high-resolution ultrasound (35 MHz) and automated analysis software, we detected dose-dependent vasodilation using established endothelium-independent [intravenous nitroglycerin EC(50) = 3.3 x 10(-6) mol/l, peak 21Delta% (SD 4)] and endothelium-dependent [intra-arterial acetylcholine EC(50) = 1.3 x 10(-6) mol/l, peak 27Delta% (SD 4)] pharmacological vasodilators. Wall shear stress induced by intra-aortic injection of adenosine and infusion of saline at increasing rates (1.5-4.5 ml/min) led to vasodilation at 1 to 2 min. Transient hindlimb ischemia by common iliac occlusion (5 min) led to reactive hyperemia with flow velocity and wall shear stress increase and was followed by FA dilation [16Delta% (SD 2)], the latter of which was completely abolished by nitric oxide synthase (NOS) inhibition with N(G)-monomethyl-L-arginine [1Delta% (SD 2)]. FMD was significantly reduced in adult 20-24-wk-old animals compared with 9- to 10-wk-old animals, consistent with age-dependent endothelial dysfunction [16Delta% (SD 3) vs. 10Delta% (SD 3), P < 0.05]. Whereas FMD was completely NOS dependent in 9- to 10-wk-old animals, NOS-dependent mechanisms accounted for only half of the FMD in 20-24-wk-old animals, with the remainder being blocked by charybdotoxin and apamin, suggesting a contribution of endothelium-derived hyperpolarizing factor. To our knowledge, this is the first integrative physiological model to reproducibly study FMD of conduit arteries in living rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / pharmacology
  • Aging / physiology
  • Animals
  • Dose-Response Relationship, Drug
  • Echocardiography*
  • Femoral Artery / diagnostic imaging
  • Femoral Artery / drug effects
  • Femoral Artery / physiology
  • Hindlimb / blood supply
  • Hyperemia / diagnostic imaging
  • Hyperemia / physiopathology
  • Ischemia / diagnostic imaging
  • Ischemia / physiopathology
  • Male
  • Nitric Oxide Synthase / physiology
  • Nitroglycerin / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology
  • Reproducibility of Results
  • Stress, Mechanical
  • Vasodilation / drug effects
  • Vasodilation / physiology*
  • Vasodilator Agents / pharmacology


  • Vasodilator Agents
  • Nitric Oxide Synthase
  • Nitroglycerin
  • Adenosine