Mineralocorticoid receptor blockade improved gut microbiota dysbiosis by reducing gut sympathetic tone in spontaneously hypertensive rats.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2023 Feb

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Microbiota has a crucial role in the host blood pressure (BP) regulation. The present study analyzes whether the mineralocorticoid receptor antagonist spironolactone ameliorates the dysbiosic state in a genetic model of neurogenic hypertension. Twenty-week-old male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were randomly allocated into three groups: untreated WKY, untreated SHR, and SHR treated with spironolactone for 5 weeks. Spironolactone restored the Firmicutes/Bacteroidetes proportion, and acetate-producing bacteria populations to WKY levels. Spironolactone reduced the percentage of intestinal aerobic bacteria. The amelioration of gut dysbiosis was linked to a reduction in the gut pathology, an enhanced colonic integrity, a reduced gut permeability and an attenuated sympathetic drive in the gut. Spironolactone was unable to reduce neuroinflammation and oxidative stress in the paraventricular nuclei in the hypothalamus. Spironolactone reduced the higher Th17 cells proportion in mesenteric lymph nodes and Th17 infiltration in aorta, improved aortic endothelial function and reduced systolic BP. This study demonstrates for the first time that spironolactone reduces gut dysbiosis in SHR. This effect could be related to its capability to improve gut integrity and pathology due to reduced sympathetic drive in the gut. Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Citation

Cristina González-Correa, Javier Moleón, Sofía Miñano, Iñaki Robles-Vera, Marta Toral, Natividad Martín-Morales, Francisco O'Valle, Manuel Sánchez, Manuel Gómez-Guzmán, Rosario Jiménez, Miguel Romero, Juan Duarte. Mineralocorticoid receptor blockade improved gut microbiota dysbiosis by reducing gut sympathetic tone in spontaneously hypertensive rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023 Feb;158:114149