ABSTRACT
BACKGROUND: 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. METHODS: 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 alpha1-catalytic subunit isoform. RESULTS: 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 micromol/min vs 14.0 +/- 0.2 micromol/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. CONCLUSIONS: 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.
