Ovine uterine space restriction causes dysregulation of the renin-angiotensin system in fetal kidneys

绵羊子宫空间受限导致胎儿肾脏肾素-血管紧张素系统失调

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作者:Rachel A Kranch-Shorthouse, Adam S Bauer, Ronald R Magness, Gladys E Lopez, Jeffrey L Segar, Sharon E Blohowiak, Pamela J Kling

Conclusions

: By late gestation, USR upregulated renal angiotensin receptor expression, an effect with potential functional implications.

Methods

: Multiparous pregnant ewes (n = 32), 16 with surgical bifurcated disconnection of one uterine horn to further reduce placental attachment sites, were studied. USR (n = 31) ovine fetuses were compared to nonspace restricted (NSR) singleton controls (n = 22) on gestational day (GD) 120 or GD130, term GD147. Fetal plasma was collected to evaluate plasma renin activity and iron indices. Fetal kidney AT 1 R, AT 2 R, and MASR proteins were assessed by Western immunoblotting and immunohistochemistry.

Objective

: To test the hypothesis that ovine USR is associated with dysregulation of the fetal renal RAS.

Results

: AT 1 R, AT 2 R, and MASR protein expression was higher in USR at GD130 than aged-matched NSR and USR at GD120, ( P < 0.05 all). AT 1 R and AT 2 R localization was homogenous throughout proximal and distal tubules in both USR and NSR at both gestational dates. MASR localization was punctate throughout renal cortical structures including tubules and glomeruli in both USR and NSR, shifted to intranuclear at GD130. Plasma renin activity was inversely related to plasma osmolarity ( P < 0.02) and was downregulated in USR at GD130 ( P < 0.05). Conclusions: : By late gestation, USR upregulated renal angiotensin receptor expression, an effect with potential functional implications.

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