Meriones unguiculatus serves as a spontaneous primary aldosteronism rodent model

Figures

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  Fig 1. MU rats develop spontaneous hypertension and hyperaldosteronism. A. Representative images of the adrenal gland appearance (scale bar = 0.5 cm) and the adrenal gland weight-to-body weight ratio of SD1 (the same body weight control), SD2 (the same age control) and MU rats. B. The systolic blood pressure (SBP) and heart rate (HR) of the SD and MU rats were measured by tail-cuff BP plethysmography (n = 10). C. Concentrations of aldosterone and renin and the aldosterone-to-renin ratio (ARR) in the serum (n = 6). D. Serum concentrations of electrolytes (n = 6). E. The amount of 24-h urine output and urinary aldosterone excretion (n = 4). F. Twenty-four-hour urinary potassium and sodium excretion (n = 4). G. Heatmap of 16 kinds of steroid hormones (n = 5). H. Representative PET/CT images of SD and MU rats. The arrow points to the adrenal gland. The results are expressed as the mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 compared with SD1 group. #P < 0.05, ##P < 0.01, ###P < 0.001, ####P < 0.0001 compared with SD2 group.

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  Fig 2. The inhibitory effect of high salt intake on the RAAS is impaired in MU rats. A. Serum concentrations of aldosterone before and after saline administration (n = 4). B-C. Serum concentration of aldosterone in SD1, SD2 and MU rats fed a normal salt diet (NSD) or a high salt diet (HSD) for 3 days (B) or 2 weeks (C) (n = 6). D. The 24-h urine output and aldosterone excretion of SD1, SD2 and MU rats fed a NSD or HSD for 2 weeks (n = 4). E. The systolic blood pressure (SBP) and heart rate (HR) of SD1, SD2 and MU rats fed a NSD or HSD for 2 weeks were measured by tail-cuff BP plethysmography (n = 10). F. The indicated cardiac parameters of SD1, SD2 and MU rats fed a NSD or HSD for 4 weeks (n = 4). G. Histological analyses of heart sections from SD1, SD2 and MU rats fed a NSD or HSD for 4 weeks. Heart cross-sections were stained with H&E to analyze hypertrophic growth (scale bar = 200 μm). The results are expressed as the mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 compared with SD1 group. #P < 0.05, ##P < 0.01, ###P < 0.001, ####P < 0.0001 compared with SD2 group. ^P < 0.05, ^^P < 0.01, ^^^P < 0.001, ^^^P < 0.0001 compared with NSD group.

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  Fig 3. The increased expression and distribution of CYP11B2 in the adrenal glands of MU rats. A. Representative western blots showing the levels of CYP11B2, CYP11B1 and HSD3B2 in the adrenal gland. The quantitative results are shown on the right (n = 4). B. Histological analyses of adrenal gland sections from SD and MU rats fed a normal or high-salt diet for 2 weeks. Adrenal gland cross-sections were stained with H&E (scale bar = 50 μm). C. Representative images showing immunohistochemical staining of CYP11B2 in the adrenal glands. Nuclei were stained with hematoxylin (scale bar = 50 μm). D. The relative proportion of CYP11B2-positive areas in the adrenal gland (n = 3). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 compared with SD1 group. #P < 0.05, ##P < 0.01, ###P < 0.001, ####P < 0.0001 compared with SD2 group. ^P < 0.05, ^^P < 0.01, ^^^P < 0.001, ^^^P < 0.0001 compared with NSD group.

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  Fig 4. The Wnt/β-catenin signaling pathway is activated in the adrenal glands of MU rats. A-C. Representative images showing immunohistochemical staining of CYP11B1 (A), Dab2 (B), and β-catenin (C) in the adrenal glands. Nuclei were stained with hematoxylin (scale bar = 50 μm). The quantitative results are shown in D (n = 3). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 compared with SD1 group. #P < 0.05, ##P < 0.01, ###P < 0.001, ####P < 0.0001 compared with SD2 group.