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

Abstract

Aim Low concentrations of NG-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