低腎単位数がマウスの高血圧感受性を高める

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.

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 RetUB del).

We discovered that adult RetUB del mice and controls have similar systolic and diastolic BP. After high salt diet, RetUB del males and females had a greater rise in systolic BP, and RetUB del females had a greater rise in diastolic BP than controls. In contrast, RetUB 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. RetUB del males had more of a CKD phenotype, suggesting that CKD did not contribute to salt-sensitivity.

This study shows the impact of a modifiable dietary factor on the development of hypertension in mice with low nephron endowment.