title: Epidermal growth factor receptor mediates the vascular dysfunction but not the remodeling induced by aldosterone/salt.
abstract: Pathophysiological aldosterone (aldo)/mineralocorticoid receptor signaling has a major impact on the cardiovascular system, resulting in hypertension and vascular remodeling. Mineralocorticoids induce endothelial dysfunction, decreasing vasorelaxation in response to acetylcholine and increasing the response to vasoconstrictors. Activation of the epidermal growth factor receptor (EGFR) is thought to mediate the vascular effects of aldo, but this has yet to be demonstrated in vivo. In this study, we analyzed the molecular and functional vascular consequences of aldo-salt challenge in the waved 2 mouse, a genetic model with a partial loss of EGFR tyrosine kinase activity. Deficient EGFR activity is associated with global oxidative stress and endothelial dysfunction. A decrease in EGFR activity did not affect the arterial wall remodeling process induced by aldo-salt. By contrast, normal EGFR activity was required for the aldo-induced enhancement of phenylephrine- and angiotensin II-mediated vasoconstriction. In conclusion, this in vivo study demonstrates that EGFR plays a key role in aldosterone-mediated vascular reactivity.
authors.affiliation: Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Violaine
authors.initials: V
authors.lastname: Griol-Charhbili
authors.forename: Céline
authors.initials: C
authors.lastname: Fassot
authors.forename: Smail
authors.initials: S
authors.lastname: Messaoudi
authors.forename: Claudine
authors.initials: C
authors.lastname: Perret
authors.forename: Vincent
authors.initials: V
authors.lastname: Agrapart
authors.forename: Frederic
authors.initials: F
authors.lastname: Jaisser
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000450:Aldosterone / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D015153:Blotting, Western; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D005838:Genotype; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009392:Nephrectomy; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; D010656:Phenylephrine; D000450:Aldosterone; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D066246:ErbB Receptors; D000109:Acetylcholine