Examinando por Autor "Aguado, Andrea"

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Pioglitazone Modulates the Vascular Contractility in Hypertension by Interference with ET-1 Pathway
(Nature Research, 2019-11-11) Palacios-Ramírez, Roberto; Hernanz, Raquel; Martín, Ángela; Pérez-Girón, Vicente; Barrús, María T; González-Carnicero, Zoe; Aguado, Andrea; Jaisser, Frederic; Briones, Ana M; Salaices, M; Alonso, MJ
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.
Pioglitazone reduces angiotensin II-induced COX-2 expression through inhibition of ROS production and ET-1 transcription in vascular cells from spontaneously hypertensive rats
(American Physiological Society, 2014-01-01) Pérez-Girón, José V; Palacios-Ramírez, R; Martín, Ángela; Hernanz, Raquel; Aguado, Andrea; Martínez-Revelles, Sonia; Barrús, María T; Salaices, Mercedes; Alonso, María J
Glitazones have anti-inﬂamma-tory properties by interfering with the transcription of proinﬂamma-tory genes, such as cyclooxygenase (COX)-2, and with ROS produc-tion, which are increased in hypertension. This study analyzedwhether pioglitazone modulates COX-2 expression in hypertension byinterfering with ROS and endothelin (ET)-1. In vivo, pioglitazone (2.5mg·kg 1 ·day 1 , 28 days) reduced the greater levels of COX-2,pre-pro-ET-1, and NADPH oxidase (NOX) expression and activity aswell as O2· production found in aortas from spontaneously hyper-tensive rats (SHRs). ANG II increased COX-2 and pre-pro-ET-1levels more in cultured vascular smooth muscle cells from hyperten-sive rats compared with normotensive rats. The ETA receptor antag-onist BQ-123 reduced ANG II-induced COX-2 expression in SHRcells. ANG II also increased NOX-1 expression, NOX activity, andsuperoxide production in SHR cells; the selective NOX-1 inhibitorML-171 and catalase reduced ANG II-induced COX-2 and ET-1transcription. ANG II also increased c-Jun transcription and phospho-JNK1/2, phospho-c-Jun, and p65 NF- B subunit nuclear proteinexpression. SP-600125 and lactacystin, JNK and NF- B inhibitors,respectively, reduced ANG II-induced ET-1, COX-2, and NOX-1levels and NOX activity. Pioglitazone reduced the effects of ANG IIon NOX activity, NOX-1, pre-pro-ET-1, COX-2, and c-Jun mRNAlevels, JNK activation, and nuclear phospho-c-Jun and p65 expres-sion. In conclusion, ROS production and ET-1 are involved in ANGII-induced COX-2 expression in SHRs, explaining the greater COX-2expression observed in this strain. Furthermore, pioglitazone inhibitsANG II-induced COX-2 expression likely by interfering with NF- Band activator protein-1 proinﬂammatory pathways and downregulat-ing ROS production and ET-1 transcription, thus contributing to theanti-inﬂammatory properties of glitazones.