First Author | Walker KA | Year | 2012 |
Journal | Am J Physiol Renal Physiol | Volume | 303 |
Issue | 2 | Pages | F253-8 |
PubMed ID | 22573381 | Mgi Jnum | J:187017 |
Mgi Id | MGI:5435125 | Doi | 10.1152/ajprenal.00028.2012 |
Citation | Walker KA, et al. (2012) High nephron endowment protects against salt-induced hypertension. Am J Physiol Renal Physiol 303(2):F253-8 |
abstractText | 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-beta2 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. |