Key result
Balb/CJ mice are more sensitive than C57BL/6J mice to angiotensin II and salt treatment, partly mediated by lower oxidative stress which favors fluid and sodium retention.
Why the study?
Balb/CJ mice develop higher mortality, edema, heart failure signs, and acute kidney injury with ANG II and high-salt diet; differences in renal gene regulation contributing to this decompensation were unknown.
In a mouse model of ANG II and salt-induced decompensation, lower oxidative stress paradoxically favors fluid and sodium retention, increasing mortality.
Mouse strain data should not guide clinical hypertension management; leaves open genetic-oxidative mechanisms for human salt sensitivity studies.
Balb/CJ mice are more sensitive to treatment with angiotensin II (ANG II) and high-salt diet compared with C57BL/6J mice. Together with higher mortality, they develop edema, signs of heart failure, and acute kidney injury. The aim of the present study was to identify differences in renal gene regulation that may affect kidney function and fluid balance, which could contribute to decompensation in Balb/CJ mice after ANG II + salt treatment. Male Balb/CJ and C57BL/6J mice were divided into the following five different treatment groups: control, ANG II, salt, ANG II + salt, and ANG II + salt + N-acetylcysteine. Gene expression microarrays were used to explore differential gene expression after treatment and between the strains. Published data from the Mouse Genome Database were used to identify the associated genomic differences. The glomerular filtration rate (GFR) was measured using inulin clearance, and fluid balance was measured using metabolic cages. Gene ontology enrichment analysis of gene expression microarrays identified glutathione transferase (antioxidant system) as highly enriched among differentially expressed genes. Balb/CJ mice had similar GFR compared with C57BL/6J mice but excreted less Na+ and water, although net fluid and electrolyte balance did not differ, suggesting that Balb/CJ mice may be inherently more prone to decompensation. Interestingly, C57BL/6J mice had higher urinary oxidative stress despite their relative protection from decompensation. In addition, treatment with the antioxidant N-acetylcysteine decreased oxidative stress in C57BL/6J mice, reduced urine excretion, and increased mortality. Balb/CJ mice are more sensitive than C57BL/6J to ANG II + salt, in part mediated by lower oxidative stress, which favors fluid and Na+ retention.
No takes yet. Share an insight, caveat, or question.
Jönsson et al. (2019) studied Angiotensin II and salt-induced decompensation. Angiotensin II and high-salt diet vs. Control, ANG II alone, salt alone, or C57BL/6J mice was evaluated on Renal gene regulation, glomerular filtration rate, and fluid balance. Balb/CJ mice are more sensitive than C57BL/6J mice to angiotensin II and salt treatment, partly mediated by lower oxidative stress which favors fluid and sodium retention.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: