Affiliation:
1. From the Institute of Clinical Pharmacology and Department of Angiology (K.A.), Medical School, Hannover, Germany.
Abstract
Background
We studied urinary nitrate and cGMP excretion rates, indices of systemic NO formation, and plasma concentrations of
l
-arginine and the endogenous NO synthase inhibitor asymmetrical dimethylarginine (ADMA) and its inactive stereoisomer, symmetrical dimethylarginine, in 77 patients with peripheral arterial occlusive disease (PAOD) in Fontaine stages IIb through IV and in 47 young and 37 elderly healthy control subjects.
Methods and Results
Urinary nitrate excretion was 182.0±11.4 μmol/mmol creatinine and cGMP excretion was 186.2±13.0 nmol/mmol creatinine in young healthy control subjects. In elderly control subjects, both excretion rates were slightly lower (nitrate, 156.0±7.8 μmol/mmol creatinine; cGMP, 150.0±8.3 nmol/mmol creatinine;
P
=NS). In PAOD patients, there was a significant, progressive reduction of urinary nitrate (IIb, 138.4±11.9; III, 128.6±11.3; and IV, 91.9±8.0 μmol/mmol creatinine;
P
<.05) and cGMP (IIb, 139.9±25.2; III, 115.6±13.1; and IV, 76.9±7.9 nmol/mmol creatinine;
P
<.05) excretion rates related to the Fontaine stage of PAOD. These changes were independent of changes in renal excretory function. Plasma
l
-arginine concentrations were not significantly different between the groups, but ADMA concentrations were elevated in PAOD patients (young control subjects, 1.25±0.11; elderly control subjects, 1.01±0.05 μmol/L; IIb, 2.62±0.24; III, 3.06±0.48; and IV, 3.49±0.26 μmol/L;
P
<.05 for PAOD versus control subjects). There was a significant linear correlation between urinary nitrate and cGMP excretion rates and a significant negative linear correlation between plasma ADMA concentrations and urinary nitrate excretion.
Conclusions
In PAOD patients, there is a progressive reduction in urinary nitrate and cGMP excretion rates, which may be caused in part by accumulation of ADMA, an endogenous inhibitor of NO synthase.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
437 articles.
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