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

• Published in: Redox biology 2019-09, Vol.26, p.101238-101238, Article 101238
• Main Authors: Liu, Taiming, Zhang, Meijuan, Mukosera, George T, Borchardt, Dan, Li, Qian, Tipple, Trent E, Ishtiaq Ahmed, Abu Shufian, Power, Gordon G, Blood, Arlin B
• Format: Article
• Language: English
• Subjects: 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; Nitric Oxide Synthase - metabolism; Nitroglycerin - pharmacology; omega-N-Methylarginine - pharmacology; Rats; Rats, Sprague-Dawley; RAW 264.7 Cells; Reactive Oxygen Species - metabolism; Research Paper; Sheep; Stereoisomerism; Vasodilation - drug effects; Vasodilation - physiology; Vasodilator Agents - pharmacology
• ISSN: 2213-2317; 2213-2317
• DOI: 10.1016/j.redox.2019.101238

L-N -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.