Asymmetric dimethylarginine reduces nitric oxide donor-mediated dilation of arterioles by activating the vascular renin-angiotensin system and reactive oxygen species

Zoltan Veresh, Bela Debreczeni, Janos Hamar, Pawel M. Kaminski, Michael S. Wolin, Akos Koller

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12 Citations (Scopus)

Abstract

Introduction: We tested the hypothesis that asymmetric dimethylarginine (ADMA) interferes with other mechanisms in addition to inhibition of nitric oxide synthase (NOS). Thus, in skeletal muscle arterioles, in the presence of ADMA, we investigated the dilator effect of an NO donor and increases in flow and aimed to elucidate the underlying mechanisms, including the role of oxidative stress, which is known to reduce the bioavailability of NO. Methods and Results: In isolated rat gracilis skeletal muscle arterioles (∼160 μm at 80 mm Hg), ADMA (similarly to pyrogallol) reduced dilations to sodium nitroprusside (SNP), which was significantly prevented by the presence of superoxide dismutase (SOD) and catalase (CAT): SNP 10 -8M; control: 43.2 ± 3%, ADMA: 4.9 ± 1%, ADMA + SOD/CAT: 30.2 ± 9% (p < 0.05). Also, ADMA reduced basal diameter and flow-induced dilations, which were not restored by L-arginine, but prevented by SOD/CAT and by inhibition of NAD(P)H oxidase (but not xanthine oxidase) and by an angiotensin-converting enzyme inhibitor or an angiotensin type 1 receptor blocker (ARB). ADMA increased the production of reactive oxygen species detected by lucigenin-enhanced chemiluminescence, which was significantly inhibited by SNP or ARB. Conclusion: We suggest that by activating the vascular renin-angiotensin-NAD(P)H oxidase pathway, ADMA elicits oxidative stress, which interferes with the bioavailability of NO and consequently reduces NO-mediated dilations.

Original languageEnglish
Pages (from-to)363-372
Number of pages10
JournalJournal of Vascular Research
Volume49
Issue number4
DOIs
Publication statusPublished - Jun 1 2012

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Keywords

  • Arteriolar dilation
  • Asymmetric dimethylarginine
  • Nitric oxide
  • Oxidative stress
  • Reactive oxygen species
  • Vascular renin-angiotensin system

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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