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Article
The Effects of Modulating Endothelial Nitric Oxide Synthase (eNOS) Activity and Coupling in Coronary, Hindlimb, Renal, and Mesenteric Vascular Inflammation Models
Research Day
  • Alexandra Lopez, Philadelphia College of Osteopathic Medicine
  • Kerry-Anne Perkins, Philadelphia College of Osteopathic Medicine
  • Amber Koon, Philadelphia College of Osteopathic Medicine
  • Amelie Bottex, Philadelphia College of Osteopathic Medicine
  • Qian Chen, Philadelphia College of Osteopathic Medicine
  • Robert Barsotti, Philadelphia College of Osteopathic Medicine
  • Lindon Young, Philadelphia College of Osteopathic Medicine
Location
Philadelphia
Start Date
13-5-2015 1:00 PM
Description
Ischemia/reperfusion (I/R) injury is initiated in part by vascular endothelial dysfunction, which is characterized by reduced endothelial-derived nitric oxide (NO) and/or increased oxidative stress, followed by inflammation. When the tetrahydrobiopterin (BH4) to dihydrobiopterin (BH2, oxidized form of BH4) ratio is reduced, eNOS can become uncoupled shifting production of NO to superoxide (SO). Protein kinase C epsilon activator (PKCε+) enhances eNOS activity while PKCε inhibitor (PKCε-) reduces eNOS activity. The effects of PKCε+ or PKCε- combined with BH4 or BH2 were studied in rat myocardial and hindlimb I/R, rat renal lithotripsy, and rat mesenteric inflammation models. Promoting eNOS coupling using PKCε+ with BH4 or inhibiting uncoupled eNOS activity using PKCε- significantly increased blood NO and decreased blood H2O2 levels in reperfused femoral and renal veins, reduced BH2-induced leukocyte-endothelial interactions in mesenteric postcapillary venules, and improved post-reperfused cardiac function associated with reduced leukocyte heart tissue infiltration when compared to controls. In contrast, PKCε+ with BH2 had opposite effects. These results suggest that enhancing coupled eNOS or inhibiting uncoupled eNOS activities can attenuate the I/R-induced vascular endothelial dysfunction, inflammation, and organ damage. This study was supported by NHLBI Grant 2R15HL-76235-02 and the CCDA at PCOM.
Citation Information
Alexandra Lopez, Kerry-Anne Perkins, Amber Koon, Amelie Bottex, et al.. "The Effects of Modulating Endothelial Nitric Oxide Synthase (eNOS) Activity and Coupling in Coronary, Hindlimb, Renal, and Mesenteric Vascular Inflammation Models" (2015)
Available at: http://works.bepress.com/qian_chen/40/