title: High nephron endowment protects against salt-induced hypertension.
abstract: While low nephron number is associated with increased risk of developing cardiovascular and renal disease, the functional consequences of a high nephron number are unknown. We tested the hypothesis that a high nephron number provides protection against hypertensive and renal insults. Mean arterial pressure (MAP) and renal function were characterized in male wild-type (WT) and transforming growth factor-β2 heterozygous (Tgfb2(+/-)) mice under basal conditions and following a chronic high-salt diet. Kidneys were collected for unbiased stereological analysis. Baseline MAP and renal function were indistinguishable between genotypes. The chronic high-salt diet (5% NaCl for 4 wk followed by 8% NaCl for 4 wk) led to similar step-wise increases in urine volume, Na(+) excretion, and albuminuria in the genotypes. The 5% NaCl diet induced modest and similar increases in MAP (3.5 ± 1.6 and 3.4 ± 0.8 mmHg in WT and Tgfb2(+/-), respectively). After the step up to the 8% NaCl diet, MAP increased further in WT (+15.9 ± 5.1 mmHg), but not Tgfb2(+/-) (-0.1 ± 1.0 mmHg), mice. Nephron number was 30% greater in Tgfb2(+/-) than WT mice and was not affected by the chronic high-salt diet. Mean glomerular volume was lower in Tgfb2(+/-) than WT mice, and the chronic high-salt diet induced significant glomerular hypertrophy. In a separate cohort of mice, an acute, 7-day, 8% NaCl diet induced similar rises in MAP in the genotypes. This is the first study to examine the physiological characteristics of a model of high nephron number, and the findings are consistent with this phenotype providing protection against chronic, but not acute, hypertensive insults.
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Walker
authors.forename: Xiaochu
authors.initials: X
authors.lastname: Cai
authors.forename: Georgina
authors.initials: G
authors.lastname: Caruana
authors.forename: Merlin C
authors.initials: MC
authors.lastname: Thomas
authors.forename: John F
authors.initials: JF
authors.lastname: Bertram
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Kett
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006579:Heterozygote; D006973:Hypertension / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009399:Nephrons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010641:Phenotype; D012965:Sodium Chloride / Q000009:adverse effects* / Q000494:pharmacology; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000502:physiology
chemical_list: C509042:Tgfb2 protein, mouse; D053781:Transforming Growth Factor beta2; D012965:Sodium Chloride