Projects per year
Abstract
Previously, we demonstrated that renal hemodynamic responses to nitric oxide (NO) inhibition were attenuated in aged, hypertensive sheep born with a solitary functioning kidney (SFK). NO is an important regulator of renal function, particularly, in the postnatal period. We hypothesized that the onset of renal dysfunction and hypertension in individuals with a SFK is associated with NO deficiency early in life. In this study, renal and cardiovascular responses to L-NAME infusion (Nw-nitro-L-arginine methyl ester) were examined in 6-month old lambs born with a SFK, induced by fetal unilateral nephrectomy (uni-x). Renal responses to L-NAME were attenuated in uni-x sheep with the fall in glomerular filtration rate (GFR) and urinary sodium excretion (UNaV) being less in the uni-x compared to sham lambs (%ΔGFR; −41 ± 3 vs −54 ± 4: P = 0.03, %ΔUNaV; −48 ± 5 vs −76 ± 3, P = 0.0008). 24 hour-basal urinary nitrate and nitrite (NOx) excretion was less in the uni-x animals compared to the sham (NOx excretion μM/min/kg; sham: 57 ± 7; uni-x: 38 ± 4, P = 0.02). L-NAME treatment reduced urinary NOx to undetectable levels in both groups. A reduction in NO bioavailability in early life may contribute to the initiation of glomerular and tubular dysfunction that promotes development and progression of hypertension in offspring with a congenital nephron deficit, including those with a SFK.
Original language | English |
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Article number | 26777 |
Number of pages | 11 |
Journal | Scientific Reports |
Volume | 6 |
DOIs | |
Publication status | Published - 26 May 2016 |
Keywords
- animal disease models
- end-stage renal disease
- experimental models of disease
- kidney diseases
Projects
- 2 Finished
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Mechanisms and consequences of renal denervation in chronic kidney disease
Denton, K., Broadhead, G. & Schlaich, M. P.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/13 → 31/12/15
Project: Research
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NHMRC Research Fellowship
National Health and Medical Research Council (NHMRC) (Australia)
1/01/08 → 31/12/17
Project: Research