Nitroso-redox balance in control of coronary vasomotor tone

Yannick Taverne, Vincent Beer, Bas Hoogteijling, RP Juni, AL Moens, Dirk-jan Duncker, Daphne Merkus

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Taverne YJ, de Beer VJ, Hoogteijling BA, Juni RP, Moens AL, Duncker DJ, Merkus D. Nitroso-redox balance in control of coronary vasomotor tone. J Appl Physiol 112: 1644-1652, 2012. First published February 23, 2012; doi:10.1152/japplphysiol.00479.2011.- Reactive oxygen species (ROS) are essential in vascular homeostasis but may contribute to vascular dysfunction when excessively produced. Superoxide anion (O-2(center dot-)) can directly affect vascular tone by reacting with K+ channels and indirectly by reacting with nitric oxide (NO), thereby scavenging NO and causing nitroso-redox imbalance. After myocardial infarction (MI), oxidative stress increases, favoring the imbalance and resulting in coronary vasoconstriction. Consequently, we hypothesized that ROS scavenging results in coronary vasodilation, particularly after MI, and is enhanced after inhibition of NO production. Chronically instrumented swine were studied at rest and during exercise before and after scavenging of ROS with N-(2-mercaptoproprionyl)-glycine (MPG, 20 mg/kg iv) in the presence or absence of prior inhibition of endothelial NO synthase (eNOS) with N-omega-nitro-L-arginine (L-NNA, 20 mg/kg iv). In normal swine, MPG resulted in coronary vasodilation as evidenced by an increased coronary venous O-2 tension, and trends toward increased coronary venous O-2 saturation and decreased myocardial O-2 extraction. These effects were not altered by prior inhibition of eNOS. In MI swine, MPG showed a significant vasodilator effect, which surprisingly was abolished by prior inhibition of eNOS. Moreover, eNOS dimer/monomer ratio was decreased after MI, reflecting eNOS uncoupling. In conclusion, ROS exert a small coronary vasoconstrictor influence in normal swine, which does not involve scavenging of NO. This vasoconstrictor influence of ROS is slightly enhanced after MI. Since inhibition of eNOS abolished rather than augmented the vasoconstrictor influence of ROS in swine with MI, while eNOS dimer/monomer ratio was decreased, our data imply that uncoupled eNOS may be a significant source of O-2(center dot-) after MI.
Original languageUndefined/Unknown
Pages (from-to)1644-1652
Number of pages9
JournalJournal of Applied Physiology
Issue number10
Publication statusPublished - 2012

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