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Angiotensin II Elicits Intracellular Ca 2+ Responses in Rat Cortical Collecting Ducts
Author(s) -
Mamenko Mykola,
Buncha Vadym,
Cherezova Alena
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.04295
Subject(s) - intracellular , angiotensin ii , chemistry , renin–angiotensin system , biophysics , microbiology and biotechnology , neuroscience , endocrinology , biology , receptor , biochemistry , blood pressure
Regulation of sodium transport in the cortical collecting duct (CCD) is pivotal for the long‐term blood pressure control and excessive Na + retention in this nephron segment is a known pathogenic determinant of hypertension. Sodium reabsorption in the CCD cells can be stimulated by volume‐regulatory hormones, such as angiotensin II (AngII). AngII reportedly binds to AT1 receptors and increases the activity of the epithelial sodium channel (ENaC) via generation of reactive oxygen species (ROS). Yet, our understanding of the exact molecular determinants mediating AngII‐induced intracellular signaling in the CCD cells remains limited. Numerous studies show that AngII induces intracellular Ca 2+ mobilization in the vasculature, cardiomyocytes and glomerular podocytes. Here, we used ratiometric Fura‐2 Ca 2+ ‐imaging to test if AngII employs Ca 2+ as a second messenger in the CCDs freshly isolated from male and female Sprague‐Dawley (SD) rats. We found that application of 500 nM of AngII to a split‐opened CCD results in a transient elevation of [Ca 2+ ] i in the CCD cells. The amplitude of the observed [Ca 2+ ] i increase is about 150 nM and is not significantly different in the CCDs isolated from male and female rats. AngII‐dependent [Ca 2+ ] i signal is not affected by removal of Ca 2+ from the extracellular bathing solution, but is practically abolished, when the tubules are pre‐incubated in 3 μM thapsigargin, indicative of Ca 2+ release from the intracellular stores. Inhibition of PLC with 10 μM U73122 markedly diminishes AngII‐induced [Ca 2+ ] i transient. Chronic AngII infusion moderately impairs [Ca 2+ ] i responses to AngII in the CCDs isolated from male rats by approximately 30%. In contrast, AngII‐induced [Ca 2+ ] i elevation is attenuated by 70% in the CCDs from AngII‐infused females. We have previously reported a stronger antihypertensive effect of aldosterone antagonism in AngII‐infused females, when compared to males. Here, we found that systemic administration of eplerenone prevents the decline of AngII‐stimulated [Ca 2+ ] i response in the CCDs from female rats with AngII‐dependent hypertension, but not in males. Overall, our data demonstrate that AngII triggers Ca 2+ release from the intracellular stores of the CCD cells in a PLC‐dependent manner. This AngII‐activated [Ca 2+ ] i mobilization is impaired in AngII‐infused SD rats of both sexes, but the attenuation is remarkably more pronounced in females. Systemic aldosterone antagonism with eplerenone restores the AngII‐mediated [Ca 2+ ] i response in the CCDs from female rats with AngII‐dependent hypertension. Future studies are granted to investigate the interplay between AngII‐dependent [Ca 2+ ] i signal and ROS generation in the CCD cells.