High doses of L‐NMMA dilate human hand veins in vivo via EDHF‐mediated mechanisms

Aim Low concentrations of N G ‐monomethyl‐L‐arginine monoacetate (L‐NMMA) are used as specific antagonists of nitric oxide synthase (eNOS). We investigated the vascular effects of high concentrations of L‐NMMA (0.2 – 6.3 μmol/min.) in dorsal human hand veins in vivo. Methods Using a parallel study design (n=10) we investigated the effects of L‐NMMA‐infusion (6.3 μmol/min) into 80% phenylephrine (PE) constricted dorsal human hand veins with (n=5) and without (n=5) coinfusion of potassium (20 mM) to inhibit EDHF's. To test potential involvement of prostacyclin, 5 additional subjects received infusions of acetylsalicylic acid (ASS), 6.25 – 296 μmolar into PE‐constricted hand veins, with and without L‐NMMA‐coinfusion (6.3 μmol/min.) in a double crossover design. Results After 70 minutes of infusion L‐NMMA increased basal vein size (BVS) from 18.2±4.2% to 38.8±6.5%. This effect was completely blocked by coinfusion of potassium resulting in 13.9±4.4% BVS. Infusion of increasing doses of ASS did not affect basal vein size (12.6±1.5% BVS at 296 μmolar ASS vs. 21.1±1.1 control) and had no influence on L‐NMMA induced venodilation (26.5±2.8% with ASS 296 μmolar vs 24.2±1.7% BVS control). Conclusion Infusion of 6.3 μmol/min L‐NMMA dilates human hand veins in vivo which can be inhibited by coinfusion of potassium suggesting that high concentrations of L‐NMMA stimulate the generation of EDHF's whereas cyclooxygenase products do not contribute. Clinical Pharmacology & Therapeutics (2004) 75 , P5–P5; doi: 10.1016/j.clpt.2003.11.018