title: Perinatal Na+ overload programs raised renal proximal Na+ transport and enalapril-sensitive alterations of Ang II signaling pathways during adulthood.
abstract: BACKGROUND
  High Na(+) intake is a reality in nowadays and is frequently accompanied by renal and cardiovascular alterations. In this study, renal mechanisms underlying perinatal Na(+) overload-programmed alterations in Na(+) transporters and the renin/angiotensin system (RAS) were investigated, together with effects of short-term treatment with enalapril in terms of reprogramming molecular alterations in kidney.
  
  
  RESULTS
  Male adult Wistar rats were obtained from dams maintained throughout pregnancy and lactation on a standard diet and drinking water (control) or 0.17 M NaCl (saline group). Enalapril (100 mg/l), an angiotensin converting enzyme inhibitor, was administered for three weeks after weaning. Ninety day old offspring from dams that drank saline presented with proximal tubules exhibiting increased (Na(+)+K(+))ATPase expression and activity. Ouabain-insensitive Na(+)-ATPase activity remained unchanged but its response to angiotensin II (Ang II) was lost. PKC, PKA, renal thiobarbituric acid reactive substances (TBARS), macrophage infiltration and collagen deposition markedly increased, and AT(2) receptor expression decreased while AT(1) expression was unaltered. Early treatment with enalapril reduced expression and activity of (Na(+)+K(+))ATPase, partially recovered the response of Na(+)-ATPase to Ang II, and reduced PKC and PKA activities independently of whether offspring were exposed to high perinatal Na(+) or not. In addition, treatment with enalapril per se reduced AT(2) receptor expression, and increased TBARS, macrophage infiltration and collagen deposition. The perinatally Na(+)-overloaded offspring presented high numbers of Ang II-positive cortical cells, and significantly lower circulating Ang I, indicating that programming/reprogramming impacted systemic and local RAS.
  
  
  CONCLUSIONS
  Maternal Na(+) overload programmed alterations in renal Na(+) transporters and in its regulation, as well as severe structural lesions in adult offspring. Enalapril was beneficial predominantly through its influence on Na(+) pumping activities in adult offspring. However, side effects including down-regulation of PKA, PKC and AT(2) receptors and increased TBARS could impair renal function in later life.
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil.
authors.forename: Edjair V
authors.initials: EV
authors.lastname: Cabral
authors.forename: Leucio D
authors.initials: LD
authors.lastname: Vieira-Filho
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Silva
authors.forename: Williams S
authors.initials: WS
authors.lastname: Nascimento
authors.forename: Regina S
authors.initials: RS
authors.lastname: Aires
authors.forename: Fabiana S T
authors.initials: FS
authors.lastname: Oliveira
authors.forename: Ricardo
authors.initials: R
authors.lastname: Luzardo
authors.forename: Adalberto
authors.initials: A
authors.lastname: Vieyra
authors.forename: Ana D O
authors.initials: AD
authors.lastname: Paixão
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000375:Aging / Q000378:metabolism / Q000502:physiology; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D027682:Cation Transport Proteins / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D036801:Parturition / Q000097:blood / Q000378:metabolism* / Q000502:physiology / Q000652:urine; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014867:Water / Q000378:metabolism; D014886:Weaning
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D027682:Cation Transport Proteins; D011945:Receptors, Angiotensin; D017392:Thiobarbituric Acid Reactive Substances; D014867:Water; D000804:Angiotensin II; D004656:Enalapril; D000803:Angiotensin I; D012964:Sodium; D003404:Creatinine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000251:Adenosine Triphosphatases; C021838:sodium-translocating ATPase; D000254:Sodium-Potassium-Exchanging ATPase