Pioglitazone Modulates the Vascular Contractility in Hypertension by Interference with ET-1 Pathway

dc.contributor.authorPalacios-Ramírez, Roberto
dc.contributor.authorHernanz, Raquel
dc.contributor.authorMartín, Ángela
dc.contributor.authorPérez-Girón, Vicente
dc.contributor.authorBarrús, María T
dc.contributor.authorGonzález-Carnicero, Zoe
dc.contributor.authorAguado, Andrea
dc.contributor.authorJaisser, Frederic
dc.contributor.authorBriones, Ana M
dc.contributor.authorSalaices, M
dc.contributor.authorAlonso, MJ
dc.date.accessioned2024-06-04T08:40:23Z
dc.date.available2024-06-04T08:40:23Z
dc.date.issued2019-11-11
dc.description.abstractEndothelin-1 (ET-1) is an important modulator of the vascular tone and a proinflammatory molecule that contributes to the vascular damage observed in hypertension. Peroxisome-proliferator activated receptors-γ (PPARγ) agonists show cardioprotective properties by decreasing inflammatory molecules such as COX-2 and reactive oxygen species (ROS), among others. We investigated the possible modulatory effect of PPARγ activation on the vascular effects of ET-1 in hypertension. In spontaneously hypertensive rats (SHR), but not in normotensive rats, ET-1 enhanced phenylephrineinduced contraction through ETA by a mechanism dependent on activation of TP receptors by COX-2- derived prostacyclin and reduction in NO bioavailability due to enhanced ROS production. In SHR, the PPARγ agonist pioglitazone (2.5 mg/Kg·day, 28 days) reduced the increased ETA levels and increased those of ETB. After pioglitazone treatment of SHR, ET-1 through ETB decreased ROS levels that resulted in increased NO bioavailability and diminished phenylephrine contraction. In vascular smooth muscle cells from SHR, ET-1 increased ROS production through AP-1 and NFκB activation, leading to enhanced COX-2 expression. These effects were blocked by pioglitazone. In summary, in hypertension, pioglitazone shifts the vascular ETA/ETB ratio, reduces ROS/COX-2 activation and increases NO availability; these changes explain the effect of ET-1 decreasing phenylephrine-induced contraction.es
dc.identifier.citationPalacios-Ramírez, R., Hernanz, R., Martín, A. et al. Pioglitazone Modulates the Vascular Contractility in Hypertension by Interference with ET-1 Pathway. Sci Rep 9, 16461 (2019). https://doi.org/10.1038/s41598-019-52839-6es
dc.identifier.doi10.1038/s41598-019-52839-6es
dc.identifier.issn2045-2322 (online)
dc.identifier.urihttps://hdl.handle.net/10115/33338
dc.language.isoenges
dc.publisherNature Researches
dc.rightsAttribution 4.0 International
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectPeroxisome-proliferator activated receptors-γ (PPARγ) agonists;COX-2;reactive oxygen species; hypertension; resistance arteries; hypertensive rats (SHR).es
dc.titlePioglitazone Modulates the Vascular Contractility in Hypertension by Interference with ET-1 Pathwayes
dc.typeinfo:eu-repo/semantics/articlees

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