Dietary sodium restriction sex-specifically impairs endothelial function via mineralocorticoid receptor-dependent reduction in NO bioavailability in Balb/C mice
| Autor: | Eric J. Belin de Chantemèle, Simone Kennard, Galina Antonova, Daisy Harwood, Jessica L. Faulkner, Nicolas Clere |
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| Přispěvatelé: | Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Nitric Oxide Synthase Type III Physiology [SDV]Life Sciences [q-bio] 030209 endocrinology & metabolism 030204 cardiovascular system & hematology Nitric Oxide Receptor Angiotensin Type 1 BALB/c 03 medical and health sciences chemistry.chemical_compound No bioavailability Sex Factors 0302 clinical medicine Mineralocorticoid receptor Dietary Sodium Physiology (medical) Internal medicine Adrenal Glands medicine Animals Cytochrome P-450 CYP11B2 Aldosterone ComputingMilieux_MISCELLANEOUS Mice Inbred BALB C biology Chemistry Diet Sodium-Restricted [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences biology.organism_classification Sodium restriction Up-Regulation Vasodilation Receptors Mineralocorticoid Endocrinology NADPH Oxidase 4 Vasoconstriction Vascular constriction Female Endothelium Vascular Cardiology and Cardiovascular Medicine Function (biology) Signal Transduction Research Article |
| Zdroj: | AJP-Heart and Circulatory Physiology AJP-Heart and Circulatory Physiology, American Physiological Society, 2020, ⟨10.1152/ajpheart.00413.2020⟩ Am J Physiol Heart Circ Physiol |
| ISSN: | 0363-6135 1522-1539 |
| DOI: | 10.1152/ajpheart.00413.2020⟩ |
| Popis: | Recent findings from our group demonstrated that females exhibit higher endothelial mineralocorticoid receptor (MR) expression than males, which predisposes them to aldosterone-mediated endothelial dysfunction in the context of metabolic disorders. However, whether the endothelium of female mice presents a higher propensity to MR-mediated dysfunction than that of males in the absence of comorbidities remains unknown. We therefore sought to investigate whether increasing aldosterone production endogenously with sodium restriction impairs endothelial function in otherwise healthy female mice. We fed male and female Balb/C mice a normal (0.4% NaCl; NSD) or sodium-restricted diet (0.05% NaCl; SRD) for 4 wk. Females exhibited higher baseline endothelial function (relaxation to acetylcholine) and lower vascular contractility (constriction to phenylephrine, serotonin, and KCl). However, SRD impaired endothelial-dependent relaxation and increased vascular contractility in female mice, effectively ablating the baseline sex difference. Female sex also increased baseline adrenal CYP11B2 expression; however, SRD significantly enhanced CYP11B2 expression in male and female mice and ablated the sex difference. Nitric oxide synthase (NOS) inhibition with N(ω)-nitro-l-arginine methyl ester hydrochloride eliminated both sex as well as diet-induced differences in endothelial dysfunction. In accordance, females demonstrated higher vascular endothelial NOS expression at baseline, which SRD significantly decreased. In addition, SRD diminished vascular NOX4 expression in female mice only. MR blockade with spironolactone-protected female mice from decreases in endothelial-dependent relaxation but not increases in vascular contractility. Utilizing sodium restriction as a method to increase plasma aldosterone levels in healthy female mice, we demonstrated that female mice are more susceptible to vascular damage via MR activation in the vascular endothelium only. NEW & NOTEWORTHY Female sex confers improved endothelial relaxation and vascular constriction responses in female Balb/C mice compared with males under baseline conditions. Sodium restriction impairs endothelial function, which is nitric oxide dependent, and increases vascular contractility in association with reduced vascular endothelial nitric oxide synthase and NOX4 expression in female mice ablating the baseline sex difference. Mineralocorticoid receptor antagonism ablates sodium restriction-induced endothelial dysfunction, but not increased vascular contractility, in female mice. |
| Databáze: | OpenAIRE |
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