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Perinatal iron deficiency and a high salt diet cause long-term kidney mitochondrial dysfunction and oxidative stress.


ABSTRACT:

Aims

Perinatal iron deficiency (ID) alters developmental trajectories of offspring, predisposing them to cardiovascular dysfunction in later life. The mechanisms underlying this long-term programming of renal function have not been defined. We hypothesized perinatal ID causes hypertension and alters kidney metabolic function and morphology in a sex-dependent manner in adult offspring. Furthermore, we hypothesized these effects are exacerbated by chronic consumption of a high salt diet.

Methods and results

Pregnant Sprague Dawley rats were fed either an iron-restricted or replete diet prior to and throughout pregnancy. Adult offspring were fed normal or high salt diets for 6 weeks prior to experimentation at 6 months of age. Blood pressure (BP) was assessed via indwelling catheters in anaesthetized offspring; kidney mitochondrial function was assessed via high-resolution respirometry; reactive oxygen species and nitric oxide were quantified via fluorescence microscopy. Adult males, but not females, exhibited increased systolic BP due to ID (P?=?0.01) and high salt intake (P?=?0.02). In males, but not in females, medullary mitochondrial content was increased by high salt (P?=?0.003), while succinate-dependent respiration was reduced by ID (P?ConclusionPerinatal ID causes long-term sex-dependent alterations in renal metabolic function and morphology, potentially contributing to hypertension and increased cardiovascular disease risk.

SUBMITTER: Woodman AG 

PROVIDER: S-EPMC6918067 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Perinatal iron deficiency and a high salt diet cause long-term kidney mitochondrial dysfunction and oxidative stress.

Woodman Andrew G AG   Mah Richard R   Keddie Danae L DL   Noble Ronan M N RMN   Holody Claudia D CD   Panahi Sareh S   Gragasin Ferrante S FS   Lemieux Helene H   Bourque Stephane L SL  

Cardiovascular research 20200101 1


<h4>Aims</h4>Perinatal iron deficiency (ID) alters developmental trajectories of offspring, predisposing them to cardiovascular dysfunction in later life. The mechanisms underlying this long-term programming of renal function have not been defined. We hypothesized perinatal ID causes hypertension and alters kidney metabolic function and morphology in a sex-dependent manner in adult offspring. Furthermore, we hypothesized these effects are exacerbated by chronic consumption of a high salt diet.<h  ...[more]

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