Improvement in renal hemodynamics following combined angiotensin II infusion and AT1R blockade in aged female sheep following fetal unilateral nephrectomy

Reetu Ragni Singh, Yugeesh Ryan Lankadeva, Katherine Maude Denton, Karen Margaret Moritz

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10 Citations (Scopus)

Abstract

Renin-angiotensin system (RAS) is a powerful modulator of renal hemodynamic and fluid homeostasis. Up-regulation in components of intra-renal RAS occurs with ageing. Recently we reported that 2 year old uninephrectomised (uni-x) female sheep have low renin hypertension and reduced renal function. By 5 years of age, these uni-x sheep had augmented decrease in renal blood flow (RBF) compared to sham. We hypothesised that this decrease in RBF in 5 year old uni-x sheep was due to an up-regulation in components of the intra-renal RAS. In this study, renal responses to angiotensin II (AngII) infusion and AngII type 1 receptor (AT1R) blockade were examined in the same 5 year old sheep. We also administered AngII in the presence of losartan to increase AngII bioavailability to the AT2R in order to understand AT2R contribution to renal function in this model. Uni-x animals had significantly lower renal cortical content of renin, AngII ( approximately 40 ) and Ang 1-7 ( approximately 60 ) and reduced cortical expression of AT1R gene than sham animals. In response to both AngII infusion and AT1R blockade via losartan, renal hemodynamic responses and tubular sodium excretion were significantly attenuated in uni-x animals compared to sham. However, AngII infusion in the presence of losartan caused approximately 33 increase in RBF in uni-x sheep compared to approximately 14 in sham (P
Original languageEnglish
Article numbere68036
Number of pages10
JournalPLoS ONE
Volume8
Issue number7
DOIs
Publication statusPublished - 2013

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