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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/H1086    most recent 00811.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Heiss, C. Articles by Springer, M. L. Search for Related Content PubMed PubMed Citation Articles by Heiss, C. Articles by Springer, M. L.

INNOVATIVE METHODOLOGY

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

¹Division of Cardiology, Department of Medicine, University of California, San Francisco, California; and ²Department of Nutrition, University of California, Davis, California

Submitted 12 July 2007 ; accepted in final form 30 November 2007

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 EC₅₀ = 3.3 x 10^–6 mol/l, peak 21% (SD 4)] and endothelium-dependent [intra-arterial acetylcholine EC₅₀ = 1.3 x 10^–6 mol/l, peak 27% (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 [16% (SD 2)], the latter of which was completely abolished by nitric oxide synthase (NOS) inhibition with N^G-monomethyl-L-arginine [1% (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 [16% (SD 3) vs. 10% (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.

nitric oxide synthase; endothelium-derived hyperpolarizing factor; rodents; age-dependent endothelial dysfunction