From the National Institutes of Health, Bethesda, Md.
Abstract—Our objectives were to (1)
test the hypothesis that nitric oxide (NO) contributes to peak reactive
hyperemia (RH) in the human peripheral vasculature,
(2) examine the impact of atherosclerosis and its risk
factors on RH, and (3) investigate whether L-arginine will
improve RH in patients with endothelial dysfunction.
The endothelium contributes to shear stress–mediated
vasomotion by releasing a variety of dilating factors, including NO,
but the contribution of NO to peak RH in patients with and without
endothelial dysfunction is unknown.
Endothelium-dependent and
endothelium-independent function was assessed with
intrafemoral arterial acetylcholine (ACh) and sodium
nitroprusside. RH was produced by occlusion of blood flow to the leg
for 3 minutes. The study was repeated after
NG-monomethyl-L-arginine
(L-NMMA) in 44 subjects and L-arginine in 9 patients with
atherosclerosis. There were 15 normal control subjects
without risk factors for atherosclerosis and 29
patients with risk factors or angiographic
atherosclerosis. Microvascular vasodilation in response
to ACh, but not to sodium nitroprusside, was lower in the patients with
risk factors or atherosclerosis compared with normal
control subjects, P=0.048, and the inhibition of
ACh-induced microvascular dilation by L-NMMA was also greater in normal
control subjects (P=0.045). Similarly, RH, including the
peak response, was inhibited by L-NMMA in normal control subjects
(P=0.0011) but not in patients with risk factors or
atherosclerosis, suggesting that the contribution of NO
to both ACh-induced dilation and RH was diminished in patients with
risk factors or atherosclerosis. L-Arginine
did not affect vasodilation in response to ACh, sodium nitroprusside,
or RH. We concluded that (1) NO contributes to all phases of RH in the
normal human peripheral vasculature, (2) patients with
atherosclerosis or its risks have abnormal NO
bioactivity in response to pharmacological and
physiological stimulation, and (3)
L-arginine does not improve RH in
atherosclerosis. Reduced
physiological vasodilation in
atherosclerosis may contribute to or exacerbate
hypertension and ischemia.
© 1998 American Heart Association, Inc.
Scientific Contributions
Contribution of Nitric Oxide to Reactive Hyperemia
Impact of Endothelial Dysfunction
Key Words: hyperemia • nitric oxide • endothelium • atherosclerosis
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