Authors: Antoine Tarjus Ekaterina Belozertseva Huguette Louis Soumaya El Moghrabi Carlos Labat Patrick Lacolley Frédéric Jaisser Guillaume Galmiche
Publish Date: 2014/09/30
Volume: 467, Issue: 8, Pages: 1643-1650
Abstract
Identification of the mineralocorticoid receptor MR in the vasculature ie endothelial and smooth muscle cells raised the question of its role in vascular function and blood pressure control Using a mouse model with conditional inactivation of MR in vascular smooth muscle cell VSMC MRSMKO we have recently shown that the VSMC MR is crucial for aldosteronesaltinduced carotid stiffening In the present study we have investigated the specific contribution of the VSMC MR in the regulation of vascular tone in large vessels In MRSMKO mice contractions induced by potassium chloride and calcium Ca2+ are decreased in the aorta whereas contraction is normal in response to phenylephrine and caffeine The difference in response to Ca2+ suggests that the VSMCspecific deficiency of the MR modifies VSM Ca2+ signaling but without altering the intracellular Ca2+ store handling The relaxation induced by acetylcholine is not affected by the absence of MR However the relaxation induced by Ach in the presence of indomethacin and the relaxation induced by sodium nitroprussiate are significantly reduced in MRSMKO mice compared to controls Since endothelial nitric oxide synthase eNOS activity is increased in mutant mice their altered relaxation reflects impairment of the nitric oxide NO signaling pathway In addition to altered NO and Ca2+ signaling the activity of myosin light chain and its regulators myosin light chain kinase MLCK and myosin phosphatase MLCP is reduced In conclusion MR expressed in VSMC is required for NO and Ca2+ signaling pathways and contractile protein activity leading to an altered contraction/relaxation couplingThis work was supported by the “Institut National pour la Santé et Recherche Médicale” and grants from the “Agence Nationale pour la Recherche” ANR09BLAN015601 the “Centre de Recherche Industrielle et Technique” and the Fondation de France A Tarjus was recipient of a PhD fellowship of the Université Pierre et Marie Curie E Belozertseva was recipient of a PhD fellowship of the “Agence Nationale pour la Recherche” ANR13BSV1002601
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