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.
Division of Cardiology, Department of Medicine, University of California, San Francisco 94143-0124, USA.
Christian
C
Heiss
Richard E
RE
Sievers
Nicolas
N
Amabile
Tony Y
TY
Momma
Qiumei
Q
Chen
Shobha
S
Natarajan
Yerem
Y
Yeghiazarians
Matthew L
ML
Springer
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