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Published on: May 15, 2009
Low nephron endowment increases susceptibility to salt-induced elevation of blood pressure in mice
Ileana Serrano Herrera1, Rushelle L Byfield1, David A Bateman1
1Department of Pediatrics.
Insights
Low nephron endowment in mice increases hypertension risk, particularly with high salt intake. This study highlights how diet impacts blood pressure in individuals with fewer nephrons, suggesting potential interventions for kidney health.
Area of Science:
- Nephrology
- Cardiovascular Physiology
- Developmental Biology
Background:
- Preterm birth is linked to reduced nephron count, increasing risks for hypertension and chronic kidney disease (CKD).
- Postnatal kidney injury exacerbates these risks in individuals with congenital nephron deficits.
- Understanding the independent effect of low nephron endowment on hypertension is crucial.
Purpose of the Study:
- To investigate if congenital low nephron endowment, independent of other renal insults, contributes to hypertension.
- To determine if salt intake modifies the blood pressure response in a low nephron endowment model.
- To explore potential sex differences in hypertension development associated with low nephron endowment.
Main Methods:
- Utilized a novel mouse model (RetUB del) with genetically reduced nephron endowment.
- Conducted continuous ambulatory blood pressure monitoring in mice.
- Assessed blood pressure responses before and after a high-salt diet challenge.
Main Results:
- Adult mice with low nephron endowment exhibited similar baseline blood pressure to controls.
- High salt diet significantly increased systolic blood pressure in both male and female RetUB del mice.
- Sex-specific differences in diastolic blood pressure response and urinary sodium excretion were observed, suggesting dimorphisms.
- RetUB del males showed a greater CKD phenotype, independent of salt-induced hypertension.
Conclusions:
- Congenital low nephron endowment is a risk factor for salt-sensitive hypertension.
- Dietary salt intake significantly impacts blood pressure in individuals with fewer nephrons.
- This study underscores the importance of modifiable dietary factors in managing hypertension risk associated with reduced nephron number.
Objectives:
Humans born preterm have low nephron endowment and an increased risk for hypertension and chronic kidney disease (CKD) later in life. The risks of these sequelae are augmented by a higher incidence of postnatal kidney injury from ischemic, hypoxic and/or nephrotoxic insults.
Methods:
To test the hypothesis that congenital nephron deficits in the absence of other renal insults are a risk factor for hypertension, and that salt intake modifies this response, we performed continuous ambulatory blood pressure (BP) monitoring before and after high salt diet in a novel mouse model of low nephron endowment (named Ret UB del ).
Results:
We discovered that adult Ret UB del mice and controls have similar systolic and diastolic BP. After high salt diet, Ret UB del males and females had a greater rise in systolic BP, and Ret UB del females had a greater rise in diastolic BP than controls. In contrast, Ret UB del males had less of a rise in diastolic BP, revealing possible sex dimorphisms in mice with low nephron endowment. In females, salt loading was accompanied by less suppression of juxtaglomerular renin and a blunted rise in fractional excretion of urinary sodium, although sample stratification reduced the power to detect significant male-female differences. Ret UB del males had more of a CKD phenotype, suggesting that CKD did not contribute to salt-sensitivity.
Conclusions:
This study shows the impact of a modifiable dietary factor on the development of hypertension in mice with low nephron endowment.
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