No abstract

BackgroundSeveral studies have correlated protein restriction associated with other nutritional deficiencies with the development of cardiovascular and renal diseases. The driving hypothesis for this study was that Ang II signaling pathways in the heart and kidney are affected by chronic protein, mineral and vitamin restriction.Methodology/Principal FindingsWistar rats aged 90 days were fed from weaning with either a control or a deficient diet that mimics those used in impoverished regions worldwide. Such restriction simultaneously increased ouabain-insensitive Na+-ATPase and decreased (Na++K+)ATPase activity in the same proportion in cardiomyocytes and proximal tubule cells. Type 1 angiotensin II receptor (AT1R) was downregulated by that restriction in both organs, whereas AT2R decreased only in the kidney. The PKC/PKA ratio increased in both tissues and returned to normal values in rats receiving Losartan daily from weaning. Inhibition of the MAPK pathway restored Na+-ATPase activity in both organs. The undernourished rats presented expanded plasma volume, increased heart rate, cardiac hypertrophy, and elevated systolic pressure, which also returned to control levels with Losartan. Such restriction led to electrical cardiac remodeling represented by prolonged ventricular repolarization parameters, induced triggered activity, early after-depolarization and delayed after-depolarization, which were also prevented by Losartan.Conclusion/SignificanceThe mechanisms responsible for these alterations are underpinned by an imbalance in the PKC- and PKA-mediated pathways, with participation of angiotensin receptors and by activation of the MAPK/ERK1/2 pathway. These cellular and molecular alterations culminate in cardiac electric remodeling and in the onset of hypertension in adulthood.

We conclude that early alterations in proximal tubule Na+ pumps, together with an abnormally augmented urinary Na+ excretion, might be the link between undernutrition and late renal dysfunction.

The present study was designed to examine the effects of EFA deficiency (EFAD) on biochemical, functional, and structural aspects of the kidney in growing and adult rats fed a normal or EFAD diet for 9 wk after weaning. Food and fluid intake (F1), urine volume, and Na+ and K+ excretions were measured weekly from weeks 4 to 8 by placing the rats in individual metabolic cages for 24 h. At week 9, Li+ and a 5% water load, respectively, were administered at 14 and 1.5 h prior to glomerular and proximal tubular function studies, as assessed by 3-h creatinine (C(Cr)) and Li+ (C(Li+)) clearances. Hematocrit and urine volume; serum and urine [Cr], [Li+], [Na+], and [K+]; and renal FA distribution were also measured. Data [corrected to 100 g/body weight (bw) and presented as means +/- SEM] were significant, at P< or = 0.05. Despite a similar ingestion of solids from weeks 4 to 7 (weeks 7 to 10 of life), the rats on the EFAD diet showed a decreased body weight from week 5. From weeks 4 to 8, Fl and urine volume were similar for both groups, but the Fl increased at week 6 in the EFAD group; 24-h Na+ and K+ excretions were similar at all weeks, except for an increase in the EFAD group for both ions at week 7. In the EFAD group, CCr and CLi+ decreased by 27 and 56.3%, respectively (385.7 +/- 33.4 vs. 280 +/- 21.1, and 21.0 +/- 2.1 vs. 9.2 +/- 1.1 microL/min/100 g; n = 9 vs. 10), the latter result suggesting increased proximal reabsorption. The 3-h Na+ and K+ excretions were similar, but the Li+ decreased (0.78 +/- 0.06 x 10(-2) vs. 0.32 +/- 0.03 x 10(-2) microeq/min/100 g) in the EFAD group, giving additional support to the suggestion. Renal structure was normal and similar for both groups, but the EFAD group showed a more prominent proximal tubule brush border, together with heavier periodic acid-Schiff staining in all specimens from weeks 5 to 9. In the EFAD group, FA of the n-9 and n-7 series were higher, but most of the n-6 series were lower as a percentage of total lipids in the medulla and cortex. Medullary levels of 20:4n-6 were maintained, 22:4n-6 declined twice, arachidonic acid was maintained, and 20:5n-3 was lower. The EFAD diet affected glomerular function, proximal tubular structure and function, and FA distribution in the rat kidney.