Reduced cholesterol levels in renal membranes of undernourished rats may account for urinary Na+ loss
- 184 Downloads
It has been demonstrated that reabsorption of Na+ in the thick ascending limb is reduced and the ability to concentrate urine can be compromised in undernourished individuals. Alterations in phospholipid and cholesterol content in renal membranes, leading to Na+ loss and the inability to concentrate urine, were investigated in undernourished rats.
Sixty-day-old male Wistar rats were utilized to evaluate (1) phospholipid and cholesterol content in the membrane fraction of whole kidneys, (2) cholesterol content and the levels of active Na+ transporters, (Na+ + K+)ATPase and Na+-ATPase, in basolateral membranes of kidney proximal tubules, and (3) functional indicators of medullary urine concentration.
Body weight in the undernourished group was 73 % lower than in control. Undernourishment did not affect the levels of cholesterol in serum or in renal homogenates. However, membranes of whole kidneys revealed 56 and 66 % reduction in the levels of total phospholipids and cholesterol, respectively. Furthermore, cholesterol and (Na+ + K+)ATPase activity in proximal tubule membranes were reduced by 55 and 68 %, respectively. Oxidative stress remained unaltered in the kidneys of undernourished rats. In contrast, Na+-ATPase activity, an enzyme with all regulatory components in membrane, was increased in the proximal tubules of undernourished rats. Free water clearance and fractional Na+ excretion were increased by 86 and 24 %, respectively, and urinary osmolal concentration was 21 % lower in undernourished rats than controls.
Life-long undernutrition reduces the levels of total phospholipids and cholesterol in membranes of renal tubular cells. This alteration in membrane integrity could diminish (Na+ + K+)ATPase activity resulting in reduced Na+ reabsorption and urinary concentrating ability.
KeywordsUndernutrition Phospholipids Kidney (Na+ + K+)ATPase Na+-ATPase Free water clearance
The authors thank Glória Costa-Sarmento for technical support and BioMedES for editing the manuscript. This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/PROCAD 519/2010), Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco, Brazilian Research Council (470740/2010-8) and Fundação Carlos Chagas Filho de Amparo à pesquisa do Estado do Rio de Janeiro, Brazil.
Conflict of interest
The authors declare that they have no conflict of interest.
- 2.Ahmed T, Rahman S, Cravioto A (2009) Oedematous malnutrition. Indian J Med Res 130:651–654Google Scholar
- 4.Hebert SC, Andreoli TE (1984) Control of NaCl transport in the thick ascending limb. Am J Physiol 246:F745–F756Google Scholar
- 10.Costa-Silva JH, Silva PA, Pedi N, Luzardo R, Einicker-Lamas M, Lara LS et al (2009) Chronic undernutrition alters renal active Na+ transport in young rats: potential hidden basis for pathophysiological alterations in adulthood? Eur J Nutr 48:437–445. doi: 10.1007/s00394-009-0032-z CrossRefGoogle Scholar
- 11.Eiam-Ong S, Sabatini S (1999) Food restriction beneficially affects renal transport and cortical membrane lipid content in rats. J Nutr 129:1682–1687Google Scholar
- 13.Eiam-Ong S, Eiam-Ong S, Sabatini S (2001) Life-long food restriction prevents renal membrane lipid deposition and lowers renal work in rats. J Med Assoc Thai 84(Suppl 1):S295–S305Google Scholar
- 14.Féraille E, Doucet A (2001) Sodium-potassium-adenosinetriphosphatase-dependent sodium transport in the kidney: hormonal control. Physiol Rev 81:345–418Google Scholar
- 17.Gomes CP, Leão-Ferreira LR, Pinheiro AA, Gomes-Quintana E, Wengert M, Lopes AG et al (2008) Crosstalk between the signaling pathways triggered by angiotensin II and adenosine in the renal proximal tubules: implications for modulation of Na+-ATPase activity. Peptides 29:2033–2038. doi: 10.1016/j.peptides.2008.07.004 CrossRefGoogle Scholar
- 18.Vieira-Filho LD, Lara LS, Silva PA, Luzardo R, Einicker-Lamas M, Cardoso HD et al (2009) Placental oxidative stress in malnourished rats and changes in kidney proximal tubule sodium ATPases in offspring. Clin Exp Pharmacol Physiol 36:1157–1163. doi: 10.1111/j.1440-1681.2009.05212.x CrossRefGoogle Scholar
- 19.Maia JCC, Gomes SL, Juliani MH (1993) Genes of antigenes of parasites. In: Morel CM (ed) A laboratory manual. Ed. Fundação Oswaldo Cruz, Rio de Janeiro, pp 146–157Google Scholar
- 20.Teodósio NR, Lago ES, Romani SA, Guedes RC (1990) A regional basic diet from northeast Brazil as a dietary model of experimental malnutrition. Arch Latinoam Nutr 40(4):533–547Google Scholar
- 24.Vieira-Filho LD, Lara LS, Silva PA, Santos FT, Luzardo R, Oliveira FS et al (2011) Placental malnutrition changes the regulatory network of renal Na-ATPase in adult rat progeny: reprogramming by maternal α-tocopherol during lactation. Arch Biochem Biophys 505:91–97. doi: 10.1016/j.abb.2010.09.025 CrossRefGoogle Scholar
- 25.Vieyra A, Nachbin L, de Dios-Abad E, Goldfeld M, Meyer-Fernandes JR, de Moraes L (1986) Comparison between calcium transport and adenosine triphosphatase activity in membrane vesicles derived from rabbit kidney proximal tubules. J Biol Chem 261:4247–4255Google Scholar
- 27.Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
- 28.Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226:497–509Google Scholar
- 29.Lima VL, Gillett MP, Silva MN, Maia M de M, Chaves Filho M (1986) Changes in the lipid composition of erythrocytes during prolonged fasting in lizard (Tropidurus torquatos) and rat (Rattus norvegicus). Comp Biochem Physiol B 83:691–695Google Scholar
- 30.Bartlett GR (1959) Colorimetric assay methods for free and phosphorylated glyceric acids. J Biol Chem 234:469–471Google Scholar
- 31.Courchaine AJ, Miller WH, Stein DB Jr (1959) Rapid semi-micro procedure for estimating free and total cholesterol. Clin Chem 5:609–614Google Scholar
- 32.Huang CJ, Fwu ML (1992) Protein insufficiency aggravates the enhanced lipid peroxidation and reduced activities of antioxidative enzymes in rats fed diets high in polyunsaturated fat. J Nutr 122:1182–1189Google Scholar
- 33.Huang CJ, Fwu ML (1993) Degree of protein deficiency affects the extent of the depression of the antioxidative enzyme activities and the enhancement of tissue lipid peroxidation in rats. J Nutr 123:803–810Google Scholar
- 34.de Souza AS, Pacheco L da C, Castro P da S, Hokoç JN, Rocha MS, do Carmo MG (2008) Brain fatty acid profiles and spatial learning in malnourished rats: effects of nutritional intervention. Nutr Neurosci 11(3):119–127. doi: 10.1179/147683008X301504
- 40.De Tomás ME, Mercuri O, Rodrigo A (1980) Effects of dietary protein and EFA deficiency on liver delta 5, delta 6 and delta 9 desaturase activities in the early developing rat. J Nutr 110(4):595–599Google Scholar
- 41.Martinez-Maldonado M, Benabe JE, Wilcox JN, Wang S, Luo C (1993) Renal renin, angiotensinogen, and ANG I-converting-enzyme gene expression: influence of dietary protein. Am J Physiol 264:F981–F988Google Scholar
- 46.Hoppe CC, Evans RG, Moritz KM, Cullen-McEwen LA, Fitzgerald SM, Dowling J et al (2007) Combined prenatal and postnatal protein restriction influences adult kidney structure, function, and arterial pressure. Am J Physiol Regul Integr Comp Physiol 292:R462–R469. doi: 10.1152/ajpregu.0079.2006 CrossRefGoogle Scholar
- 51.Peil AE, Stolte H, Schmidt-Nielsen B (1990) Uncoupling of glomerular and tubular regulations of urea excretion in rat. Am J Physiol 258:F1666–F1674Google Scholar