Pioglitazone Modulates the Vascular Contractility in Hypertension by Interference with ET-1 Pathway
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 suc...
| Autores: | , , , , , , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Recursos: | Universidad Rey Juan Carlos |
| Repositorio: | BURJC-Digital. Repositorio Institucional de la Universidad Rey Juan Carlos |
| OAI Identifier: | oai:burjcdigital.urjc.es:10115/33338 |
| Acesso em linha: | https://hdl.handle.net/10115/33338 |
| Access Level: | acceso abierto |
| Palavra-chave: | Peroxisome-proliferator activated receptors-γ (PPARγ) agonists COX-2 reactive oxygen species hypertension resistance arteries |
| Resumo: | 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. |
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