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Hypertension increases contractile responses to hydrogen peroxide in resistance arteries through increased thromboxane A2, Ca2+, and superoxide anion levels

dc.contributor.authorGarcía-Redondo, AB
dc.contributor.authorBriones, AM
dc.contributor.authorBeltrán, A
dc.contributor.authorAlonso, MJ
dc.contributor.authorSimonsen, U
dc.contributor.authorSalaices, M
dc.identifier.citationJ Pharmacol Exp Ther. 2009 Jan;328(1):19-27es
dc.description.abstractThis study investigated the mechanisms underlying the response to hydrogen peroxide (H2O2) in mesenteric resistance arteries from spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto (WKY) rats. Arteries were mounted in microvascular myographs for isometric tension recording and for simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i), superoxide anion (O2.-) production was evaluated by dihydroethidium fluorescence and confocal microscopy, and thromboxane A2 (TXA2) production was evaluated by enzyme immunoassay. H2O2 (1¿100 microM) induced biphasic responses characterized by a transient endothelium-dependent contraction followed by relaxation. Simultaneous measurements of tension and Ca2+ showed a greater effect of H2O2 in arteries from hypertensive than normotensive rats. The cyclooxygenase (cox) inhibitor, indomethacin [1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1-H-indole-3-acetic acid] (1 microM); the COX-1 inhibitor, SC-58560 [5-(4-chlorophenyl)- 1-(4-methoxyphenyl)-3-trifluoromethyl pyrazole] (1 microM); the thromboxane (TXA2) synthase inhibitor, furegrelate [5-(3- pyridinylmethyl)-2-benzofurancarboxylic acid, sodium salt] (10 microM); and the TXA2/prostaglandin H2 receptor antagonist, SQ 29,548 ([1S-[1.alpha.,2.alpha.(Z),3.alpha.,4.alpha.]]-7-[3-[[2 [(phenylamino) carbonyl] hydrazino] methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5- heptenoic acid)) (1 microM) abolished H2O2 contraction in arteries from WKY rats but only reduced it in SHRs. The O2.- scavenger, tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid disodium salt) (1 mM), and the NADPH oxidase inhibitor, apocynin (4¿- hydroxy-3¿-methoxyacetophenone) (0.3 mM), decreased H2O2 contraction in arteries from SHRs but not in WKY rats. H2O2 induced TXA2 and O2.- production that was greater in SHRs than in WKY rats. The TXA2 analog, U46619 [9,11-di-deoxy-11alpha,9alpha-epoxymethano prostaglandin F2alpha (0.1 nM¿1 microM)], also increased O2.- production in SHR vessels. H2O2-induced TXA2 production was decreased by SC-58560. H2O2-induced O2.- production was decreased by tiron, apocynin, and SQ 29,548. In conclusion, the enhanced H2O2 contraction in resistance arteries from SHRs seems to be mediated by increased TXA2 release from COX-1 followed by elevations in vascular smooth muscle [Ca2+]i levels and O2.- production. This reveals a new mechanism of oxidative stress-induced vascular damage in
dc.subjectBiología y Biomedicinaes
dc.titleHypertension increases contractile responses to hydrogen peroxide in resistance arteries through increased thromboxane A2, Ca2+, and superoxide anion levelses
dc.subject.unesco2411.03 Fisiología Cardiovasculares
dc.description.departamentoCiencias de la Salud III

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