Affiliation:
1. From the Institute of Clinical Pharmacology (S.M.B.-B., R.H.B., D.H., D.T., J.C.F.) and Department of Angiology (H.A., A.C., K.A.), Medical School, Hannover, Germany.
Abstract
Background
l
-Arginine is the precursor of endogenous nitric oxide (NO), which is a potent vasodilator acting via the intracellular second-messenger cGMP. In healthy humans,
l
-arginine induces peripheral vasodilation and inhibits platelet aggregation due to an increased NO production. Prostaglandin E
1
(PGE
1
) induces peripheral vasodilation via stimulating prostacyclin receptors.
Methods and Results
We investigated the effects of one intravenous infusion of
l
-arginine (30 g, 60 minutes) or PGE
1
(40 μg, 60 minutes) versus those of placebo (150 mL 0.9% saline, 60 minutes) on blood pressure, peripheral hemodynamics, and urinary NO
3
−
and cGMP excretion rates in patients with critical limb ischemia (peripheral arterial occlusive disease stages Fontaine III or IV). Blood flow in the femoral artery was significantly increased by
l
-arginine (+42.3±7.9%,
P
<.05) and by PGE
1
(+31.0±10.2%,
P
<.05) but not by placebo (+4.3±13.0%,
P
=NS). Urinary NO
3
−
excretion increased by 131.8±39.5% after
l
-arginine (
P
<.05) but only by 32.3±17.2% after PGE
1
(
P
=NS). Urinary cGMP excretion increased by 198.7±84.9% after
l
-arginine (
P
<.05) and by 94.2±58.8% after PGE
1
(
P
=NS). Both urinary index metabolites were unchanged by placebo.
Conclusions
We conclude that intravenous
l
-arginine induces NO-dependent peripheral vasodilation in patients with critical limb ischemia. These effects are paralleled by increased urinary NO
3
−
and cGMP excretion, indicating an enhanced systemic NO production. Increased urinary NO
3
−
excretion may be a sum effect of NO synthase substrate provision (
l
-arginine) and increased shear stress (PGE
1
and
l
-arginine).
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
166 articles.
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