Chronic undernutrition alters renal active Na+ transport in young rats: potential hidden basis for pathophysiological alterations in adulthood?
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Epidemiological studies in the northeastern region of Brazil show an association between hypertension and malnutrition, especially in areas where protein-deficient diets are combined with high salt intake.
Aims of study
We studied the consequences of a widely consumed deficient diet (basic regional diet, BRD), combined with high NaCl, on growth, renal Na+ and water handling and activities of ATP-dependent Na+ transporters in kidney proximal tubules.
Young rats were fed after weaning with a low-protein and high-salt diet, which mimics that used in a vast region of Brazil. Body mass was evaluated from weaning up to the 19th week of age. Glomerular filtration rate, proximal Na+ reabsorption, distal Na+ delivery, urinary excretion of Na+ and water, and urine concentration capacity were evaluated from serum and urine concentrations of creatinine, Na+ and Li+, and by measurement of urinary volume and density. The (Na+ + K+)ATPase and the ouabain-insensitive Na+-ATPase were studied in vitro by measuring ATP hydrolysis. Expression of (Na+ + K+)ATPase was evaluated by immunodetection with the use of a specific antibody anti α1-catalytic subunit isoform.
Undernourished rats reached early adulthood (14 weeks) with body and renal masses that were 2.3 times lower than controls. These rats became hypertensive (mean arterial pressure 18.7 ± 0.6 kPa vs 15.5 ± 0.9 kPa in control group) and showed augmented fractional proximal Na+ reabsorption (61.0 ± 0.3% vs 81.8 ± 2.2%) with a concomitant decrease in distal Na+ delivery (9.5 ± 0.5 μmol/min vs 14.0 ± 0.2 μmol/min per 100 g body weight). Urinary Na+ excretion was higher in BRD rats, (juvenile and adult) being however twice the increase in Na+ intake. The ATP-dependent Na+ transporters were affected in opposite ways. The (Na+ + K+)ATPase activity from undernourished rats fell by 30%, in parallel with a 20% decrease in its immunodetection, whereas the ouabain-insensitive Na+-ATPase, which is responsible for the fine-tune control of Na+ reabsorption, increased threefold.
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.
KeywordsChronic undernutrition (Na+ + K+)ATPase Na+-ATPase Renal sodium handling Alterations in renal transporters
The skillful technical assistance of Glória Costa-Sarmento, José Paulo Soares and Gilsandro J. Barbosa da Silva is acknowledged. This research was supported by grants from the Brazilian Research Council (CNPq), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), the Rio de Janeiro State Research Foundation (to Marcelo Einicker-Lamas and Adalberto Vieyra) and the José Bonifácio Foundation (to Lucienne S. Lara). João H. Costa-Silva and Nadir Pedi were recipients of a fellowship from CNPq; Paulo A. Silva and Ricardo Luzardo were recipients of a fellowship from CAPES.
Conflict of interest
None of the authors have any conflict of interest.
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