Characterization of an inhibitor of nitric oxide synthase in human-hand veins

• Published in: Hormone and metabolic research Vol. 26; no. 2; p. 109
• Main Authors: Bedarida, G V, Kim, D, Blaschke, T F, Hoffman, B B
• Format: Journal Article
• Language: English
• Published: Germany 01-02-1994
• Subjects: Adult; Amino Acid Oxidoreductases - antagonists & inhibitors; Arginine - analogs & derivatives; Arginine - pharmacology; Bradykinin - antagonists & inhibitors; Bradykinin - pharmacology; Hand - blood supply; Humans; Male; Methylene Blue; Muscle, Smooth, Vascular - enzymology; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; Nitric Oxide Synthase; omega-N-Methylarginine; Phenylephrine - pharmacology; Regional Blood Flow - drug effects; Vascular Resistance - drug effects; Vasodilation - drug effects; Veins - enzymology
• ISSN: 0018-5043
• DOI: 10.1055/s-2007-1000784

The enzyme nitric oxide synthase mediates synthesis of nitric oxide (NO) from 1-arginine in endothelial cells. NO, also known as endothelium-dependent relaxing factor (EDRF), diffuses to smooth muscle cells where it leads to cGMP production and dilation. We characterized the potency, efficacy and time course of NG-monomethyl-l-arginine (l-NMMA) as an inhibitor of bradykinin-mediated, endothelium-dependent dilation using the human hand-vein compliance technique. We also compared the efficacy of l-NMMA with methylene blue, an inhibitor of guanylate cyclase, in blocking bradykinin-mediated vasodilation. l-NMMA potently inhibited bradykinin-induced venodilation with a log ED50 of 3.74 +/- 0.52 (geometric mean of 5.5 micrograms/min). Responses to bradykinin (0.27-555 ng/min) were tested in veins pre-constricted with the alpha-adrenergic agonist phenylephrine. l-NMMA (25 micrograms/min) decreased bradykinin's maximal venodilatory response from 90 +/- 22% to 39 +/- 15% (p < 0.05). Complete recovery of bradykinin venodilation was obtained within 155 minutes after stopping l-NMMA infusion, indicating that its effects were reversible. In another set of experiments we compared the efficacy of methylene blue to l-NMMA; methylene blue decreased bradykinin-mediated venodilatory response to 53 +/- 17%; when l-NMMA was added, the response was further decreased to 32 +/- 9% (p < 0.002). We conclude that l-NMMA is a very efficacious NO synthase inhibitor in human veins and it is likely functionally reversible.