When aldosterone production is inappropriate for the level of salt, it is pathogenic, and hypertensive subjects with inappropriate levels have increased target organ damage and a greater odds ratio for cardiovascular disease than do patients with hypertension of unknown cause ( 3, 4). Aldosterone raises blood pressure and enhances renal Na reabsorption and K excretion. We conclude that native ZG cells are electrical oscillators, and that this behavior provides what we believe to be a new molecular explanation for the control of Ca 2+ entry in these steroidogenic cells.Īutonomous overproduction of aldosterone, termed primary hyperaldosteronism (PA), is the most common form of endocrine hypertension (13% incidence), but among patients with resistant hypertension, its incidence increases substantially to 20% ( 1, 2). This innate electrical excitability of ZG cells provides a platform for the production of a recurrent Ca 2+ signal that can be controlled by Ang II and extracellular potassium, the 2 major regulators of aldosterone production. Here, we show that mouse ZG cells within adrenal slices spontaneously generate membrane potential oscillations of low periodicity. Although sustained production of aldosterone requires persistent Ca 2+ entry through low-voltage activated Ca 2+ channels, isolated ZG cells are considered nonexcitable, with recorded membrane voltages that are too hyperpolarized to permit Ca 2+ entry. When dysregulated, aldosterone is pathogenic and contributes to the development and progression of cardiovascular and renal disease. All rights reserved.Aldosterone, which plays a central role in the regulation of blood pressure, is produced by zona glomerulosa (ZG) cells of the adrenal gland. Copyright © 2022 Wolters Kluwer Health, Inc. The relation with the development of aldosterone-producing adenoma remains to be determined. This is seen in both adrenals and therefore suggests a common process. We demonstrate a decrease in CYP11B2 area and continuity, whilst the mean gap length and maximum CYP11B2 depth increases, which we consider as involution and clustering of the zG. The intraclass correlation coefficient between both adrenals of one subject for CYP11B2 expressing area was 0.78 (95%CI = 0.56–0.89), for CYP11B2 continuity 0.94 (95%CI = 0.88–0.97) and for mean gap length 0.76 (95%CI = 0.32–0.81). 30, P = <0.001) and no correlation between age and mean CYP11B2 depth (rs =. There was a negative correlation between age and CYP11B2 expressing area (rs = -.63) negative correlation between age and CYP11B2 continuity (rs = -.80) positive correlation with age and mean gap length (rs = 0.71) positive correlation between age and maximum CYP11B2 depth (rs =. The study was approved by the local Medical Ethics Committee. We also determined the structural similarity between both adrenals of the same case. If the zG was discontinuous, mean length of ‘gaps’ between ZG tissue was calculated.
We then used this automated method to quantify CYP11B2 expressing area, CYP11B2 continuity and mean and maximum CYP11B2 depth.
#Zona glomerulosa software
We validated software for automated quantification by comparing manually outlined CYP11B2 expressing area with automated outlined area. In case of two available adrenals in one patient, one was randomly selected of the two. We excluded adrenal glands of patients with premature birth, hypertension, cardiovascular disease, adrenal tumors, use of steroids. We collected human adrenals from autopsy cases, that were anonymized except for age, sex and medical history. Therefore, the objective of this study was to elucidate age-related changes of the zG by quantifying CYP11B2 expression in adrenals of patients below the age of 40 years. Research on age-related changes in the zG in younger patients and comparison of both adrenals is limited. Studies demonstrate that the area and continuity of the zG decreases with aging and accumulations of aldosterone-producing cell clusters occur. Antibodies to CYP11B2 (aldosterone synthase) allow imaging of the zona glomerulosa (zG) by immunohistochemistry.
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