Asymmetric Dimethylarginine Reduces Nitric Oxide Donor-Mediated Dilation of Arterioles by Activating the Vascular Renin-Angiotensin System and Reactive Oxygen Species

作者：Veresh Zoltan^*; Debreczeni Bela; Hamar Janos; Kaminski Pawel M; Wolin Michael S; Koller Akos

来源：Journal of Vascular Research, 2012, 49(4): 363-372.

DOI：10.1159/000337485

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

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 (similar to 160 mu m 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(-8) to; control: 43.2 +/- 3%, ADMA: 4.9 +/- 1%, ADMA + SOD/CAT: 30.2 +/- 9% (p %26lt; 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.

• 出版日期2012