Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease

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. Urinary nitrate excretion was 182.0+/-11.4 micromol/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 micromol/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 micromol/mmol creatinine; P