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Differential Regulation of TRPV1 Channels in the Murine Coronary Vasculature by H2O2

Kmetz, John George, II
http://rave.ohiolink.edu/etdc/view?acc_num=kent1398336723

Abstract Details

2014, MS, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
A critical amount of reactive oxygen species (ROS) contributes to coronary blood flow (CBF) regulation; however, oxidative stress (OS) impairs CBF regulation and is elevated in diabetes. We have previously demonstrated TRPV1- dependent coupling of CBF to metabolism is disrupted in diabetic cardiomyopathy (DCM). Accordingly, we hypothesized that basal levels of H2O2 stimulate TRPV1 whereas enhanced oxidative stress desensitizes and/or deactivates TRPV1 indirectly via a mechanism involving the lipid peroxidation product 4-Hydroxy-2-nonenal (4-HNE). H2O2 caused robust dilation in control coronary microvessels (blunted in the presence of the TRPV1 inhibitor SB366791 and in TRPV1-/- vessels), suggesting H2O2 - induced vasodilation occurs in part via TRPV1. Acute exposure to H2O2 potentiates capsaicin – mediated (TRPV1 agonist) vasodilation while a prolonged exposure to H2O2 eliminates this TRPV1 – dependent response. Interestingly, coronary microvessels isolated from db/db mice exhibit diminished H2O2 – induced coronary dilation when compared to controls remaining consistent with our previous findings. Lastly, coronary microvessels isolated from control mice incubated with 4-HNE demonstrate reduced TRPV1 – dependent coronary vasoreactivity. These data suggest low levels of H2O2 can potentiate TRPV1 activation. However, increased ROS concentrations, as seen in DCM, can lead to enhanced 4-HNE levels which modulate TRPV1 and disrupt its signaling. Thus, H2O2 – mediated differential regulation of TRPV1 could provide insight into the mechanism responsible for the uncoupling of myocardial blood flow (MBF) to metabolism associated with diabetes and DCM.
Ian Bratz, PhD (Advisor)
William Chilian, PhD (Committee Chair)
Charles Thodeti, PhD (Committee Member)
Derek Damron, PhD (Committee Member)
98 p.
Biomedical Research
TRPV1, 4-HNE, Reactive Oxygen Species, H2O2, Cardiovascular disease, Diabetic cardiomyopathy, Oxidative Stress, Microvascular Disease

Recommended Citations

Citations

  • Kmetz, II, J. G. (2014). Differential Regulation of TRPV1 Channels in the Murine Coronary Vasculature by H2O2 [Master's thesis, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1398336723

    APA Style (7th edition)

  • Kmetz, II, John. Differential Regulation of TRPV1 Channels in the Murine Coronary Vasculature by H2O2. 2014. Kent State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1398336723.

    MLA Style (8th edition)

  • Kmetz, II, John. "Differential Regulation of TRPV1 Channels in the Murine Coronary Vasculature by H2O2." Master's thesis, Kent State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=kent1398336723

    Chicago Manual of Style (17th edition)

kent1398336723
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© 2014, some rights reserved.Creative Commons License Differential Regulation of TRPV1 Channels in the Murine Coronary Vasculature by H2O2 by John George Kmetz II is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Kent State University and OhioLINK.