Pioglitazone Modulates the Vascular Contractility in Hypertension by Interference with ET-1 Pathway
dc.contributor.author | Palacios-Ramírez, Roberto | |
dc.contributor.author | Hernanz, Raquel | |
dc.contributor.author | Martín, Ángela | |
dc.contributor.author | Pérez-Girón, Vicente | |
dc.contributor.author | Barrús, María T | |
dc.contributor.author | González-Carnicero, Zoe | |
dc.contributor.author | Aguado, Andrea | |
dc.contributor.author | Jaisser, Frederic | |
dc.contributor.author | Briones, Ana M | |
dc.contributor.author | Salaices, M | |
dc.contributor.author | Alonso, MJ | |
dc.date.accessioned | 2024-06-04T08:40:23Z | |
dc.date.available | 2024-06-04T08:40:23Z | |
dc.date.issued | 2019-11-11 | |
dc.description.abstract | Endothelin-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.citation | Palacios-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/s41598-019-52839-6 | es |
dc.identifier.doi | 10.1038/s41598-019-52839-6 | es |
dc.identifier.issn | 2045-2322 (online) | |
dc.identifier.uri | https://hdl.handle.net/10115/33338 | |
dc.language.iso | eng | es |
dc.publisher | Nature Research | es |
dc.rights | Attribution 4.0 International | |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Peroxisome-proliferator activated receptors-γ (PPARγ) agonists;COX-2;reactive oxygen species; hypertension; resistance arteries; hypertensive rats (SHR). | es |
dc.title | Pioglitazone Modulates the Vascular Contractility in Hypertension by Interference with ET-1 Pathway | es |
dc.type | info:eu-repo/semantics/article | es |
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