Prenatally programmed hypertension induced by maternal protein restriction is associated with increased expression of the renal tubular Na+/K+/2Cl− co-transporter (NKCC2) and the Na+/Cl− co-transporter (NCC). This has led to the suggestion that renal Na+ retention contributes to the development of hypertension in the LP rat (offspring exposed to a maternal low-protein diet in utero). However, this hypothesis has not been tested in vivo. Renal clearance measurements in hypertensive 4-week-old male and female LP rats showed that, although the glomerular filtration rate remained unaltered, urine flow (P<0.01) and urinary Na+ excretion rates (1.6±0.3 and 3.0±0.4 μmol·min−1·100 g−1 of body weight in control male and LP male respectively; P<0.001) were increased. Na+ excretion was positively correlated with mean arterial pressure in both males (P<0.01) and females (P<0.05), but neither the slope nor the intercept differed between control and LP rats. Fractional excretion of Na+ was increased in male (1.5±0.2 and 3.0±0.5% in control and LP rats respectively; P<0.001) and female LP rats, implying reduced tubular reabsorption of Na+. Western blotting and quantitative PCR showed that NKCC2 expression was increased, whereas NCC mRNA was not up-regulated. Na+/K+ ATPase α1 subunit expression did not differ from controls; however, there was a significant reduction in whole kidney pump activity (23.4±1.8 and 17.7±1.2 nmol of phosphate·μg−1 of protein·h−1 in control male and male LP rats respectively; P<0.001); immunohistochemistry showed that the α1 subunit was virtually absent from the inner medulla. The greater Na+ excretion of LP rats can be explained, in part, by a pressure–natriuresis mechanism; however, the loss of the Na+/K+ ATPase α1 subunit from the inner medulla and up-regulation of NKCC2 suggests that altered renal Na+ handling is also programmed prenatally.
Research Article| June 15 2009
Prenatal programming of renal sodium handling in the rat
Saleh H. Alwasel;
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Saleh H. Alwasel, Nick Ashton; Prenatal programming of renal sodium handling in the rat. Clin Sci (Lond) 1 July 2009; 117 (2): 75–84. doi: https://doi.org/10.1042/CS20080294
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