Renal Nitric Oxide Deficiency and Chronic Kidney Disease in Young Sheep Born with a Solitary Functioning Kidney
| Autor: | Lindsea C. Booth, Geoffrey A. Head, Lawrence K. Easton, Kate M. Denton, Karen M. Moritz, Markus P. Schlaich, Reetu R. Singh |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Hypertension Renal Urinary system Renal function Nephron 030204 cardiovascular system & hematology Kidney Nitric Oxide Article Renal Circulation End stage renal disease Solitary Kidney 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Humans Renal Insufficiency Chronic Nitrates Sheep Multidisciplinary Renal circulation business.industry Hemodynamics Kidney metabolism medicine.disease Disease Models Animal NG-Nitroarginine Methyl Ester 030104 developmental biology medicine.anatomical_structure Endocrinology Female Nitric Oxide Synthase business Glomerular Filtration Rate Kidney disease |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep26777 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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