title: Characterization of local vascular effects of the nitric oxide inhibitor NG-monomethyl-L-arginine on dorsal hand veins.
abstract: Infusion of NG-monomethyl-L-arginine (L-NMMA; 6.4 µmol/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 µmol/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(2α)-(PGF(2α))-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(2α)-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 µmol/min and continuous PE-induced α-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.
authors.affiliation: Institute of Clinical Pharmacology, Medical Faculty, Technical University Dresden, Fiedlerstrasse 27, D-01307 Dresden, Germany. christoph.schindler@tu-dresden.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Schindler
authors.forename: Sven
authors.initials: S
authors.lastname: Leuschner
authors.forename: Uta
authors.initials: U
authors.lastname: Schwanebeck
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Kirch
mesh_terms: D000328:Adult; D001120:Arginine / Q000378:metabolism; D012898:Autacoids / Q000378:metabolism; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006225:Hand / Q000098:blood supply*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D013237:Stereoisomerism; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects* / Q000378:metabolism; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D012898:Autacoids; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III