L-NAME releases nitric oxide and potentiates subsequent nitroglycerin-mediated vasodilation.

Abstract

L-NG-Nitro arginine methyl ester (L-NAME) has been widely applied for several decades in both basic and clinical research as an antagonist of nitric oxide synthase (NOS). Herein, we show that L-NAME slowly releases NO from its guanidino nitro group. Daily pretreatment of rats with L-NAME potentiated mesenteric vasodilation induced by nitrodilators such as nitroglycerin, but not by NO. Release of NO also occurred with the NOS-inactive enantiomer D-NAME, but not with L-arginine or another NOS inhibitor L-NMMA, consistent with the presence or absence of a nitro group in their structure and their nitrodilator-potentiating effects. Metabolic conversion of the nitro group to NO-related breakdown products was confirmed using isotopically-labeled L-NAME. Consistent with Fenton chemistry, transition metals and reactive oxygen species accelerated the release of NO from L-NAME. Both NO production from L-NAME and its nitrodilator-potentiating effects were augmented under inflammation. NO release by L-NAME can confound its intended NOS-inhibiting effects, possibly by contributing to a putative intracellular NO store in the vasculature.

• Authors: Taiming Liu, Meijuan Zhang, George T Mukosera, Dan Borchardt, Qian Li, Trent E Tipple, Abu Shufian Ishtiaq Ahmed, Gordon G Power, Arlin B Blood
• Journal: Redox biology (Redox Biol) Vol. 26 Pg. 101238 (09 2019) ISSN: 2213-2317 [Electronic] Netherlands
• PMID: 31200239 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Enzyme Inhibitors
• Reactive Oxygen Species
• Vasodilator Agents
• omega-N-Methylarginine
• Nitric Oxide
• Arginine
• Nitric Oxide Synthase
• Nitroglycerin
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Arginine (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Female
• Mesenteric Arteries (drug effects)
• Mice
• Myography
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (antagonists & inhibitors, metabolism)
• Nitroglycerin (pharmacology)
• RAW 264.7 Cells
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Sheep
• Stereoisomerism
• Vasodilation (drug effects, physiology)
• Vasodilator Agents (pharmacology)
• omega-N-Methylarginine (pharmacology)