In vivo measurement of flow-mediated vasodilation in living rats using high-resolution ultrasound.
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.
Heiss
Christian
C
Division of Cardiology, Department of Medicine, University of California, San Francisco 94143-0124, USA.
Sievers
Richard E
RE
Amabile
Nicolas
N
Momma
Tony Y
TY
Chen
Qiumei
Q
Natarajan
Shobha
S
Yeghiazarians
Yerem
Y
Springer
Matthew L
ML
D000241:Adenosine / Q000494:pharmacology; D000375:Aging / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply; D006940:Hyperemia / Q000000981:diagnostic imaging / Q000503:physiopathology; D007511:Ischemia / Q000000981:diagnostic imaging / Q000503:physiopathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D015203:Reproducibility of Results; D013314:Stress, Mechanical; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; D000241:Adenosine