title: Renal Nitric Oxide Deficiency and Chronic Kidney Disease in Young Sheep Born with a Solitary Functioning Kidney.
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 (N(w)-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.
authors.affiliation: Cardiovascular Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Australia.
authors.forename: Reetu R
authors.initials: RR
authors.lastname: Singh
authors.affiliation: Cardiovascular Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Australia.
authors.forename: Lawrence K
authors.initials: LK
authors.lastname: Easton
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Melbourne Australia.
authors.forename: Lindsea C
authors.initials: LC
authors.lastname: Booth
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Markus P
authors.initials: MP
authors.lastname: Schlaich
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Head
authors.affiliation: School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Moritz
authors.affiliation: Cardiovascular Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Australia.
authors.forename: Kate M
authors.initials: KM
authors.lastname: Denton
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005919:Glomerular Filtration Rate; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006977:Hypertension, Renal / Q000209:etiology / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000172:deficiency*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012079:Renal Circulation / Q000187:drug effects; D051436:Renal Insufficiency, Chronic / Q000209:etiology* / Q000503:physiopathology; D012756:Sheep; D000075529:Solitary Kidney / Q000151:congenital / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D009566:Nitrates; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester