Hydrogen peroxide potentiates the EDHF phenomenon by promoting endothelial Ca2+ mobilization

Edwards, David, Li, Yiwen and Griffith, Tudor Morley 2011. Hydrogen peroxide potentiates the EDHF phenomenon by promoting endothelial Ca2+ mobilization. Arteriosclerosis Thrombosis and Vascular Biology 28 (10) , pp. 1774-1781. 10.1161/ATVBAHA.108.172692

Preview

PDF - Published Version Download (1MB) | Preview

Abstract

Objective— The purpose of this study was to test the hypothesis that H2O2 contributes to the EDHF phenomenon by mobilizing endothelial Ca2+ 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 KCa channels and were potentiated by exogenous H2O2 and the thiol oxidant thimerosal. Preincubation with a submaximal concentration of CPA unmasked an ability of exogenous H2O2 to stimulate an EDHF-type response that was sensitive to KCa channel blockade. Imaging of cytosolic and endoplasmic reticulum [Ca2+] in rabbit aortic valve endothelial cells with Fura-2 and Mag-fluo-4 demonstrated that H2O2 and thimerosal, which sensitizes the InsP3 receptor, both enhanced CPA-evoked Ca2+ release from stores, and that the potentiating effect of H2O2 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 43Gap26, which interrupts intercellular communication via gap junctions constructed from connexin 43. Conclusions— H2O2 can enhance EDHF-type relaxations by potentiating Ca2+ release from endothelial stores, probably via redox modification of the InsP3 receptor, leading to the opening of hyperpolarizing endothelial KCa channels and an electrotonically-mediated relaxant response.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QP Physiology R Medicine > R Medicine (General)
Uncontrolled Keywords:	hydrogen peroxide; thimerosal; SERCA pump; EDHF
Additional Information:	Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/1079-5642/ (accessed 19/02/2014).
Publisher:	American Heart Association, Inc.
ISSN:	1079-5642
Date of First Compliant Deposit:	30 March 2016
Last Modified:	26 May 2023 12:48
URI:	https://orca.cardiff.ac.uk/id/eprint/27665

Citation Data

Cited 58 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item