TY - JOUR
T1 - High nephron endowment protects against salt-induced hypertension
AU - Walker, Kenneth A
AU - Cai, Xiaochu
AU - Caruana, Georgina
AU - Thomas, Merlin C
AU - Bertram, John F
AU - Kett, Michelle M
PY - 2012
Y1 - 2012
N2 - Whilst 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 insults. Mean arterial pressure (MAP) and renal function were characterised in male WT and Tgfb2(+/-) mice under basal conditions and following chronic high salt diet. Kidneys were collected for unbiased stereological analysis. Baseline MAP and renal function were indistinguishable between genotypes. Chronic high NaCl diet (5 for 4 weeks, then step-up to 8 for 4 weeks) 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 (WT 3.5 +/- 1.6mmHg; Tgfb2(+/-) 3.4 +/- 0.8mmHg). Following the step up to 8 NaCl diet, MAP increased further in WT (+15.9 +/- 5.1mmHg), but not Tgfb2(+/-) mice (-0.1 +/- 1.0mmHg). Nephron number was 30 greater in Tgfb(+/-) compared to WT mice and was not affected by chronic high NaCl. Mean glomerular volume was lower in Tgfb2(+/-) compared to WT mice and chronic high NaCl diet induced significant glomerular hypertrophy. In a separate cohort of mice, the responses to 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.
AB - Whilst 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 insults. Mean arterial pressure (MAP) and renal function were characterised in male WT and Tgfb2(+/-) mice under basal conditions and following chronic high salt diet. Kidneys were collected for unbiased stereological analysis. Baseline MAP and renal function were indistinguishable between genotypes. Chronic high NaCl diet (5 for 4 weeks, then step-up to 8 for 4 weeks) 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 (WT 3.5 +/- 1.6mmHg; Tgfb2(+/-) 3.4 +/- 0.8mmHg). Following the step up to 8 NaCl diet, MAP increased further in WT (+15.9 +/- 5.1mmHg), but not Tgfb2(+/-) mice (-0.1 +/- 1.0mmHg). Nephron number was 30 greater in Tgfb(+/-) compared to WT mice and was not affected by chronic high NaCl. Mean glomerular volume was lower in Tgfb2(+/-) compared to WT mice and chronic high NaCl diet induced significant glomerular hypertrophy. In a separate cohort of mice, the responses to 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.
UR - http://ajprenal.physiology.org/content/303/2/F253.full.pdf
U2 - 10.1152/ajprenal.00028.2012
DO - 10.1152/ajprenal.00028.2012
M3 - Article
SN - 1522-1466
VL - 303
SP - F253 - F258
JO - American Journal of Physiology-Renal Physiology
JF - American Journal of Physiology-Renal Physiology
IS - 2
ER -