Characterization of Local Vascular Effects of the Nitric Oxide Inhibitor NG-Monomethyl-L-Arginine on Dorsal Hand Veins

Infusion of NG-monomethyl-L-arginine (L-NMMA; 6.4 mu mol/min) into hand veins can cause a 20% increase in vein size in specific subjects. This study explored potential underlying mechanisms in healthy male participants. Ten healthy male participants received in phenylephrine (PE)-preconstricted veins a dose-response curve (DRC) to L-NMMA (0.2-6.4 mu mol/min) without and with coinfusion of the endothelium-dependent dilator histamine, a DRC to L-arginine with and without coinfusion of L-NMMA, a DRC to NG-monomethyl-D-arginine (D-NMMA), and a DRC to L-NMMA in prostaglandin F-2 alpha-(PGF(2 alpha))-preconstricted veins. Participants were classified as L-NMMA responders (R) and nonresponders (NR). Infusion of L-NMMA resulted in a maximum venodilation of 38% +/- 11% (R) versus 10% +/- 5% (NR; P = .005). In PGF(2 alpha)-preconstricted veins, L-NMMA caused venodilation to 26% +/- 34% (NS) in responders. Results suggest that endothelial nitric oxide synthase-mediated formation of nitric oxide (NO) from L-NMMA in doses >3.2 mu mol/min and continuous PE-induced alpha-adrenergic stimulation resulting in release of very small amounts of NO from L-NMMA contribute to the observed L-NMMA-induced increase in vein size. Venous reactivity to L-NMMA resulting in a phenotype as R or NR is most likely genetically predetermined, which requires further study.