期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 294, 期 2, 页码 H1086-H1093出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00811.2007
关键词
nitric oxide synthase; endothelium-derived hyperpolarizing factor; rodents; age-dependent endothelial dysfunction
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 Delta% (SD 4)] and endothelium-dependent [intra-arterial acetylcholine EC50 = 1.3 x 10(-6) mol/l, peak 27 Delta% (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 Delta% (SD 2)], the latter of which was completely abolished by nitric oxide synthase (NOS) inhibition with N-G-monomethyl-L-arginine [1 Delta% (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 Delta% (SD 3) vs. 10 Delta% (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.
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