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Rôles physiopathologiques des récepteurs corticostéroïdes dans le rein et dans l'endothélium vasculaire : apports des modèles conditionnels transgéniques

Abstract : Corticosteroids hormones (mineralocorticoids and glucocorticoids) play a major role in blood pressure regulation. Indeed, mineralocorticoids receptors (MR) and glucocorticoids receptors (GR) are transcriptional factors which control renal sodium reabsorption and potassium excretion. However, in vivo functional studies analyzing the respective role of MR and GR remain difficult due to both receptors co-expression in the kidney, the heart and the vessels, as well as due to their comparable affinity to different binding-ligands. The goal of my thesis is to study the respective role of MR and GR receptors in the kidney and in the vascular endothelium. We generated conditional transgenic mice models which overexpress either the MR or the GR in a tissue-specific manner. We demonstrated for the first time that GR overexpression specifically in the renal collecting duct (CD) leads to specific effects of GR in the regulation of sodium homeostasis through modification of expression of different ion channels and their regulators. Our results highlight compensatory changes occurring in the upstream distal and connecting tubule that limit the functional effects of GR overexpression in the CD. The conditional overexpression of the MR in the endothelium induces a mild hypertension, an increase in vascular contractility associated with modifications in calcium-activated potassium channels expression, without any change in vascular structural parameters. This demonstrates a role of aldosterone in blood pressure control independently of renal ionic homeostasis.
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https://tel.archives-ouvertes.fr/tel-00812420
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Submitted on : Friday, April 12, 2013 - 10:11:24 AM
Last modification on : Wednesday, October 14, 2020 - 3:58:26 AM
Long-term archiving on: : Saturday, July 13, 2013 - 4:02:27 AM

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  • HAL Id : tel-00812420, version 1

Citation

Aurélie Nguyen Dinh Cat. Rôles physiopathologiques des récepteurs corticostéroïdes dans le rein et dans l'endothélium vasculaire : apports des modèles conditionnels transgéniques. Physiologie [q-bio.TO]. Université Pierre et Marie Curie - Paris VI, 2008. Français. ⟨NNT : 2008PA066203⟩. ⟨tel-00812420⟩

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