dc.contributor.author | Tomasova, L | |
dc.contributor.author | Pavlovicova, M | |
dc.contributor.author | Malekova, L | |
dc.contributor.author | Misak, A | |
dc.contributor.author | Kristek, F | |
dc.contributor.author | Grman, M | |
dc.contributor.author | Cacanyiova, S | |
dc.contributor.author | Tomasek, M | |
dc.contributor.author | Tomaskova, Z | |
dc.contributor.author | Perry, Alexis | |
dc.contributor.author | Wood, ME | |
dc.contributor.author | Lacinova, L | |
dc.contributor.author | Ondrias, K | |
dc.contributor.author | Whiteman, Matthew | |
dc.date.accessioned | 2015-03-25T15:29:42Z | |
dc.date.issued | 2015-04-30 | |
dc.description.abstract | H2S donor molecules have the potential to be viable therapeutic agents. The aim of this current study was (i) to investigate the effects of a novel triphenylphosphonium derivatised dithiolethione (AP39), in the presence and absence of reduced nitric oxide bioavailability and (ii) to determine the effects of AP39 on myocardial membrane channels; CaV3, RyR2 and Cl(-). Normotensive, L-NAME- or phenylephrine-treated rats were administered Na2S, AP39 or control compounds (AP219 and ADT-OH) (0.25-1 µmol kg(-1)i.v.) and haemodynamic parameters measured. The involvement of membrane channels T-type Ca(2+) channels CaV3.1, CaV3.2 and CaV3.3 as well as Ca(2+) ryanodine (RyR2) and Cl(-) single channels derived from rat heart sarcoplasmic reticulum were also investigated. In anaesthetised Wistar rats, AP39 (0.25-1 µmol kg(-1) i.v) transiently decreased blood pressure, heart rate and pulse wave velocity, whereas AP219 and ADT-OH and Na2S had no significant effect. In L-NAME treated rats, AP39 significantly lowered systolic blood pressure for a prolonged period, decreased heart rate and arterial stiffness. In electrophysiological studies, AP39 significantly inhibited Ca(2+) current through all three CaV3 channels. AP39 decreased RyR2 channels activity and increased conductance and mean open time of Cl(-) channels. This study suggests that AP39 may offer a novel therapeutic opportunity in conditions whereby (•)NO and H2S bioavailability are deficient such as hypertension, and that CaV3, RyR2 and Cl(-) cardiac membrane channels might be involved in its biological actions. | en_GB |
dc.description.sponsorship | Slovak Research and Development Agency | en_GB |
dc.description.sponsorship | BMBS COST Action | en_GB |
dc.identifier.citation | Vol. 46, pp. 131 - 144 | en_GB |
dc.identifier.doi | 10.1016/j.niox.2014.12.012 | |
dc.identifier.grantnumber | APVV-0074-11 | en_GB |
dc.identifier.grantnumber | 2/0050/13 | en_GB |
dc.identifier.grantnumber | 2/0094/12 | en_GB |
dc.identifier.grantnumber | 2/0044/13 | en_GB |
dc.identifier.grantnumber | BM1005 | en_GB |
dc.identifier.other | S1089-8603(14)00519-9 | |
dc.identifier.uri | http://hdl.handle.net/10871/16618 | |
dc.language.iso | en | en_GB |
dc.publisher | Elsevier | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pubmed/25555533 | en_GB |
dc.rights.embargoreason | Publisher's policy | en_GB |
dc.rights | NOTICE: this is the author’s version of a work that was accepted for publication in Nitric Oxide. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Nitric Oxide, 2015, Vol.46, pp. 131-144 DOI: 10.1016/j.niox.2014.12.012 | en_GB |
dc.subject | AP39 | en_GB |
dc.subject | Blood pressure | en_GB |
dc.subject | H(2)S | en_GB |
dc.subject | Nitric oxide deficiency | en_GB |
dc.subject | Pulse wave velocity | en_GB |
dc.title | Effects of AP39, a novel triphenylphosphonium derivatised anethole dithiolethione hydrogen sulfide donor, on rat haemodynamic parameters and chloride and calcium Cav3 and RyR2 channels. | en_GB |
dc.type | Article | en_GB |
exeter.place-of-publication | United States | |
dc.description | Copyright © 2014 Elsevier Inc. All rights reserved. | en_GB |
dc.identifier.journal | Nitric Oxide | en_GB |