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Segmental sodium reabsorption by the renal tubule in prenatally programmed hypertension in the rat

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Abstract

Hypertension and renal dysfunction can be programmed in the rat by prenatal exposure to a low-protein (LP) diet. Expression of the renal thick ascending limb (TAL) sodium transporter NKCC2 is up-regulated, which has been predicted to result in greater sodium reabsorption. However, we have shown that LP rats excrete more not less sodium. The aim of this study was to determine whether the increased abundance of sodium:potassium:chloride (Na+:K+:2Cl-) co-transporter (NKCC2) leads to enhanced sodium uptake by the TAL. Pregnant Wistar rats were fed a control (18%) or LP (9%) diet. Amiloride (AM), bendroflumethiazide (BF), and furosemide (FUR) were administered acutely to male offspring at 4 weeks of age. Fractional excretion of sodium (FENa) was significantly greater in vehicle-infused LP rats (3.0 ± 0.3%) compared with controls (1.7 ± 0.5, P < 0.01). FENa by the LP proximal tubule did not differ from controls, whereas FENa by the distal tubule was significantly greater (P < 0.01). These differences were abolished by the administration of AM + BF (equivalent to the outflow from the TAL) and AM + BF + FUR (equivalent to the outflow from the proximal tubule), suggesting that the increase in NKCC2 expression was not functional. However, during acute salt loading, the LP rat pressure natriuresis curve was shifted rightward, implying that raised systemic blood pressure is required to match urinary sodium excretion with dietary intake. These data suggest that renal sodium handling is impaired in the LP rat but that this is not due to increased NKCC2 expression.

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Funding

This work was supported by funds from the Fetal Programming of Diseases Research Chair, King Saud University, Saudi Arabia (SHA).

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Authors and Affiliations

  1. Fetal Programming of Diseases Research Chair, College of Science, King Saud University, PO Box 2455, Riyadh, 11451, Saudi Arabia

    Saleh H. Alwasel

  2. Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia

    Saleh H. Alwasel

  3. Center of Excellence in Biotechnology Research, King Saud University, Riyadh, Saudi Arabia

    Saleh H. Alwasel

  4. Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK

    Nick Ashton

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  1. Saleh H. Alwasel
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  2. Nick Ashton
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Correspondence to Saleh H. Alwasel.

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Alwasel, S.H., Ashton, N. Segmental sodium reabsorption by the renal tubule in prenatally programmed hypertension in the rat. Pediatr Nephrol 27, 285–293 (2012). https://doi.org/10.1007/s00467-011-1976-9

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  • DOI: https://doi.org/10.1007/s00467-011-1976-9

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