Récepteurs AT1-AT2 de l'angiotensine II et propriétés particulières des antagonistes AT1 sur la circulation cérébrale chez le rat

Abstract : The Renin Angiotensin System plays a major role in cerebral circulation. AT1 receptor blockers (ARBs) afford protection against cerebrovascular complications that go beyond that to be expected from their blood pressure lowering action. Several mechanisms could explain such beneficial effects. Firstly, by blocking AT1 receptors, ARBs promote AT2 receptor stimulation by angiotensin II. The beneficial effect related to stimulation of AT2 receptors (vasodilation) counterbalances the deleterious actions of AT1 receptors stimulation. Changes in this ratio may then alter cerebral circulation. We demonstrated that the AT1- AT2 ratio is modified at the cerebrovascular level during high salt intake, which is a risk factor for stroke. The AT2-mediated vasodilation of pial arterioles is abolished. Secondly, some ARBs act as partial agonists of PPAR-gamma. Such an activity, which has been demonstrated to protect extracerebral vessels, could also be beneficial for cerebral circulation. Our results showed that PPAR-gamma activation improves ARB effects on cerebral circulation (arteriolar diameter, angiotensin II reactivity). The underlying mechanisms could imply functional regulation of AT1-AT2 receptors without any change in expression status. AT2 receptor stimulation and PPAR-gamma activity are two special properties of ARBs. These properties could contribute to the cerebroprotection induced by ARBs, beyond the AT1-receptor blockade. Development of new molecules with AT1-receptor blockade and PPAR-gamma activity could take part into the future therapeutic management of hypertension, providing a better cerebrovascular protection
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Theses
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http://docnum.univ-lorraine.fr/prive/DDOC_T_2012_0002_FOULQUIER.pdf
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https://hal.univ-lorraine.fr/tel-01749146
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Submitted on : Thursday, March 29, 2018 - 12:07:43 PM
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  • HAL Id : tel-01749146, version 1

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Sébastien Foulquier. Récepteurs AT1-AT2 de l'angiotensine II et propriétés particulières des antagonistes AT1 sur la circulation cérébrale chez le rat. Médecine humaine et pathologie. Université de Lorraine, 2012. Français. ⟨NNT : 2012LORR0002⟩. ⟨tel-01749146⟩

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