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

Singh, Reetu R., Lankadeva, Yugeesh R., Denton, Kate M. and Moritz, Karen M. (2013) Improvement in renal hemodynamics following combined angiotensin II infusion and AT1R blockade in aged female sheep following fetal unilateral nephrectomy. PLoS ONE, 8 7: e68036.1-e68036.10. doi:10.1371/journal.pone.0068036


Author Singh, Reetu R.
Lankadeva, Yugeesh R.
Denton, Kate M.
Moritz, Karen M.
Title Improvement in renal hemodynamics following combined angiotensin II infusion and AT1R blockade in aged female sheep following fetal unilateral nephrectomy
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-07-01
Sub-type Article (original research)
DOI 10.1371/journal.pone.0068036
Open Access Status DOI
Volume 8
Issue 7
Start page e68036.1
End page e68036.10
Total pages 10
Place of publication United States
Publisher Public Library of Science
Collection year 2014
Language eng
Formatted 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 (~40%) and Ang 1–7 (~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 ~33% increase in RBF in uni-x sheep compared to ~14% in sham (P<0.05). This was associated with a significant decrease in renal vascular resistance in the uni-x animals (22% vs 15%, P<0.05) without any changes in systemic blood pressure. The present study shows that majority of the intra-renal RAS components are suppressed in this model of low renin hypertension. However, increasing the availability of AngII to AT2R by AT1R blockade improved renal blood flow in uni-x sheep. This suggests that manipulation of the AT2R maybe a potential therapeutic target for treatment of renal dysfunction associated with a congenital nephron deficit.
Keyword Low-protein diet
Reduced nephron number
Living kidney donors
Blood-pressure
Adult sheep
Prenatal exposure
Glucocorticoid treatment
Antenatal betamethasone
Cardiovascular-disease
Arterial-pressure
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
 
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