title: Prenatal programming of renal sodium handling in the rat.
abstract: 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 mumol.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 alpha1 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.mug-1 of protein.h-1 in control male and male LP rats respectively; P<0.001); immunohistochemistry showed that the alpha1 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 alpha1 subunit from the inner medulla and up-regulation of NKCC2 suggests that altered renal Na+ handling is also programmed prenatally.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Saleh H
authors.initials: SH
authors.lastname: Alwasel
authors.forename: Nick
authors.initials: N
authors.lastname: Ashton
mesh_terms: D000818:Animals; D005260:Female; D005333:Fetus / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000196:embryology / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D015222:Sodium Channels; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase