High nephron endowment protects against salt-induced hypertension

Kenneth A Walker, Xiaochu Cai, Georgina Caruana, Merlin C Thomas, John F Bertram, Michelle M Kett

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22 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)F253 - F258
Number of pages6
JournalAmerican Journal of Physiology-Renal Physiology
Issue number2
Publication statusPublished - 2012

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