title: Urine-concentrating defects exacerbate with age in male offspring with a low-nephron endowment.
abstract: Fetal uninephrectomy (uni-x) in male sheep at 100 days of gestation (term = 150 days) reduces overall nephron endowment without affecting birth weight. Offspring have a lower glomerular filtration rate (GFR) and elevated mean arterial pressure (MAP) at 6 mo of age. This study investigated whether this reduction in renal function was associated with impaired urine-concentrating ability at 6 mo of age and exacerbated with ageing (4 yr) and examined response to 1) nonpressor dose of exogenous arginine vasopressin (AVP; 0.2 μg·kg(-1)·h(-1) iv) and 2) 30 h of water deprivation. Basal MAP was higher in uni-x animals at both ages, and became further elevated with age compared with the sham group (elevation in MAP with age; sham: ~4 mmHg, uni-x: 9 mmHg, P(group × age) < 0.01). GFR declined with ageing in both groups with the decrease being greater with age in the uni-x group (further 26%, P(group × age) < 0.001). In response to AVP infusion, urine osmolality increased in both treatment groups; this response was significantly lower in the uni-x animals and became further reduced with ageing. Uni-x animals had reduced renal expression of vasopressin-2 receptor and aquaporin-2 at both ages (P < 0.01). The increase in plasma AVP levels in response to dehydration was similar between the treatment groups, suggesting the urine-concentrating defect was associated with these renal gene changes rather than defects in AVP secretion. Renal insufficiency due to a low-nephron endowment increases the risk of hypertension and chronic renal disease and may incur greater vulnerability to physiological challenges such as water deprivation as observed in the uni-x animals.
authors.affiliation: School of Biomedical Sciences, University of Queensland, St. Lucia, 4067 QLD, Australia.
authors.forename: Reetu R
authors.initials: RR
authors.lastname: Singh
authors.forename: Kate M
authors.initials: KM
authors.lastname: Denton
authors.forename: John F
authors.initials: JF
authors.lastname: Bertram
authors.forename: John
authors.initials: J
authors.lastname: Dowling
authors.forename: Karen M
authors.initials: KM
authors.lastname: Moritz
mesh_terms: D000367:Age Factors; D000818:Animals; D050034:Antidiuretic Agents / Q000494:pharmacology; D051399:Aquaporin 2 / Q000096:biosynthesis; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003681:Dehydration / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D007671:Kidney Concentrating Ability / Q000502:physiology*; D008297:Male; D009392:Nephrectomy; D009399:Nephrons / Q000187:drug effects / Q000502:physiology*; D017483:Receptors, Vasopressin / Q000096:biosynthesis; D012756:Sheep
chemical_list: D050034:Antidiuretic Agents; D051399:Aquaporin 2; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin