Fetal uninephrectomy in male sheep alters the systemic and renal responses to angiotensin II infusion and AT1R blockade

Singh, Reetu R., Moritz, Karen M., Wintour, E. Marelyn, Jefferies, Andrew J., Iqbal, Javed, Bertram, John F. and Denton, Kate M. (2011) Fetal uninephrectomy in male sheep alters the systemic and renal responses to angiotensin II infusion and AT1R blockade. American Journal of Physiology-Renal Physiology, 301 2: F319-F326. doi:10.1152/ajprenal.00139.2011

Author Singh, Reetu R.
Moritz, Karen M.
Wintour, E. Marelyn
Jefferies, Andrew J.
Iqbal, Javed
Bertram, John F.
Denton, Kate M.
Title Fetal uninephrectomy in male sheep alters the systemic and renal responses to angiotensin II infusion and AT1R blockade
Journal name American Journal of Physiology-Renal Physiology   Check publisher's open access policy
ISSN 1931-857X
Publication date 2011-08
Sub-type Article (original research)
DOI 10.1152/ajprenal.00139.2011
Volume 301
Issue 2
Start page F319
End page F326
Total pages 8
Place of publication United States
Publisher American Physiological Society
Collection year 2012
Language eng
Formatted abstract
Fetal uninephrectomy (uni-x) at 100 days of gestation results in compen satory nephrogenesis in the remaining kidney, resulting in a 30% reduction in total nephron number in male sheep. Recently, we showed that uni-x males at 6 mo of age have elevated arterial pressure, reduced renal blood flow (RBF), glomerular filtration rate (GFR), and low plasma renin levels (Singh R, Denton K, Bertram J, Jefferies A, Head G, Lombardo P, Schneider-Kolsky M, Moritz K. J Hypertens 27: 386-396, 2009; Singh R, Denton K, Jefferies A, Bertram J, Moritz K. Clin Sci (Lond) 118: 669-680, 2010). We hypothesized this was due to upregulation of the intrarenal renin-angiotensin system (RAS). In this study, renal responses to ANG II infusion and ANG II type 1 receptor (AT1R) blockade were examined in the same 6-mo-old male sheep. Uni-x animals had reduced levels of renal tissue and plasma renin and ANG II. Renal gene expression of renin, and gene and protein levels of AT1R and AT2R, were significantly lower in uni-x animals. In response to graded ANG II infusion, sham animals had the expected decrease in conscious RBF and GFR. Interestingly, the response was biphasic in uni-x sheep, with GFR initially decreasing, but then increasing at higher ANG II doses (34 ± 7%; Pgroup × treatment < 0.001), due to a paradoxical decrease in renal vascular resistance (Pgroup × treatment, < 0.001). In response to AT1R blockade, while GFR and group X treatment RBF responded similarly between groups, there was a marked increase in sodium excretion in uni-x compared with sham sheep (209 ± 35 vs. 25 ± 12%; P < 0.001). In conclusion, in 6-mo-old male sheep born with a single kidney, these studies demonstrate that this is a low-renin form of hypertension, in which responses to ANG II are perturbed and the intrarenal RAS is downregulated. © 2011 by the American Physiological Society.
Keyword Hypertension
Nephron number
Ang II
Intrarenal RAS
Fetal programming
Maternal Protein Restriction
Reduced Nephron Number
Adult-Blood Pressure
Unilateral Nephrectomy
Prenatal Exposure
Sympathetic Activity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
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