| 18669883 |
Edwards DH, Li Y, Griffith TM: Hydrogen peroxide potentiates the EDHF phenomenon by promoting endothelial Ca2+ mobilization. Arterioscler Thromb Vasc Biol. 2008 Oct;28(10):1774-81. Epub 2008 Jul 31.
OBJECTIVE: The purpose of this study was to test the hypothesis that H (2) O (2) contributes to the EDHF phenomenon by mobilizing endothelial Ca (2+) stores. METHODS AND RESULTS: Myograph studies with rabbit iliac arteries demonstrated that EDHF-type relaxations evoked by the SERCA inhibitor cyclopiazonic acid (CPA) required activation of K (Ca) channels and were potentiated by exogenous H (2) O (2) and the thiol oxidant thimerosal. Preincubation with a submaximal concentration of CPA unmasked an ability of exogenous H (2) O (2) to stimulate an EDHF-type response that was sensitive to K (Ca) channel blockade. Imaging of cytosolic and endoplasmic reticulum [Ca (2+)] in rabbit aortic valve endothelial cells with Fura-2 and Mag-fluo-4 demonstrated that H (2) O (2) and thimerosal, which sensitizes the InsP (3) receptor, both enhanced CPA-evoked Ca (2+) release from stores, and that the potentiating effect of H (2) O (2) was suppressed by the cell-permeant thiol reductant glutathione monoethylester. CPA-evoked relaxations were attenuated by exogenous catalase and potentiated by the catalase inhibitor 3-aminotriazole, and were abolished by the connexin-mimetic peptide (43) Gap26, which interrupts intercellular communication via gap junctions constructed from connexin 43. CONCLUSIONS: H (2) O (2) can enhance EDHF-type relaxations by potentiating Ca (2+) release from endothelial stores, probably via redox modification of the InsP (3) receptor, leading to the opening of hyperpolarizing endothelial K (Ca) channels and an electrotonically-mediated relaxant response. |
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