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A role for the sodium pump in H2O2-induced vasorelaxation in porcine isolated coronary arteries

Wong, P.S.; Garle, M.J.; Alexander, S.P.H.; Randall, M.D.; Roberts, R.E.

Authors

P.S. Wong

M.J. Garle



Abstract

Hydrogen peroxide (H2O2) has been proposed to act as a factor for endothelium-derived hyperpolar-ization (EDH) and EDH may act as a ‘back up’ system to compensate the loss of the NO pathway. Here,the mechanism of action of H2O2in porcine isolated coronary arteries (PCAs) was investigated. DistalPCAs were mounted in a wire myograph and pre-contracted with U46619 (1 nM–50 muM), a throm-boxane A2-mimetic or KCl (60 mM). Concentration–response curves to H2O2(1 muM–1 mM), bradykinin(0.01 nM–1 muM), sodium nitroprusside (SNP) (10 nM–10 muM), verapamil (1 nM–10 muM), KCl (0–20 mM)or Ca2+-reintroduction (1 muM–10 mM) were constructed in the presence of various inhibitors. Activityof the Na+/K+-pump was measured through rubidium-uptake using atomic absorption spectropho-tometry. H2O2caused concentration-dependent vasorelaxations with a maximum relaxation (Rmax) of100 ± 16% (mean ± SEM), pEC50= 4.18 ± 0.20 (n = 4) which were significantly inhibited by PEG-catalase at0.1–1.0 mM H2O2(P < 0.05). 10 mM TEA significantly inhibited the relaxation up to 100 muM H2O2(P < 0.05).60 mM K+and 500 nM ouabain significantly inhibited H2O2-induced vasorelaxation producing a relax-ation of 40.8 ± 8.5% (n = 5) and 47.5 ± 8.6% (n = 6) respectively at 1 mM H2O2(P < 0.0001). H2O2-inducedvasorelaxation was unaffected by the removal of endothelium, inhibition of NO, cyclo-oxygenase, gapjunctions, SKCa, IKCa, BKCaKir, KV, KATPor cGMP. 100 muM H2O2had no effects on the KCl-induced vasore-laxation or Ca2+-reintroduction contraction. 1 mM H2O2inhibited both KCl-induced vasorelaxation andrubidium-uptake consistent with inhibition of the Na+/K+-pump activity. We have shown that the vas-cular actions of H2O2are sensitive to ouabain and high concentrations of H2O2are able to modulate theNa+/K+-pump. This may contribute towards its vascular actions.

Citation

Wong, P., Garle, M., Alexander, S., Randall, M., & Roberts, R. (2014). A role for the sodium pump in H2O2-induced vasorelaxation in porcine isolated coronary arteries. Pharmacological Research, 90, doi:10.1016/j.phrs.2014.09.004

Journal Article Type Article
Acceptance Date Sep 14, 2014
Online Publication Date Sep 26, 2014
Publication Date Dec 3, 2014
Deposit Date Aug 3, 2016
Journal Pharmacological Research
Print ISSN 1043-6618
Electronic ISSN 1043-6618
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 90
DOI https://doi.org/10.1016/j.phrs.2014.09.004
Keywords Hydrogen peroxide (H2O2) relaxation; Ouabain-sensitive sodium–potassium pump; KCl relaxation; Rubidium uptake; Ca2+-reintroduction; Porcine coronary artery
Public URL http://eprints.nottingham.ac.uk/id/eprint/35683
Publisher URL http://www.sciencedirect.com/science/article/pii/S1043661814001480
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0