title: Renal molecular mechanisms underlying altered Na+ handling and genesis of hypertension during adulthood in prenatally undernourished rats.
abstract: In the present study, we investigated the development of hypertension in prenatally undernourished adult rats, including the mechanisms that culminate in dysfunctions of molecular signalling in the kidney. Dams were fed a low-protein multideficient diet throughout gestation with or without α-tocopherol during lactation. The time course of hypertension development followed in male offspring was correlated with alterations in proximal tubule Na+-ATPase activity, expression of angiotensin II (Ang II) receptors, and activity of protein kinases C and A. After the establishment of hypertension, Ang II levels, cyclo-oxygenase 2 (COX-2) and NADPH oxidase subunit expression, lipid peroxidation and macrophage infiltration were examined in renal tissue. Lipid peroxidation in undernourished rats, which was very intense at 60 d, decreased at 90 d and returned to control values by 150 d. During the prehypertensive phase, prenatally undernourished rats exhibited elevated renal Na+-ATPase activity, type 2 Ang II receptor down-regulation and altered protein kinase A:protein kinase C ratio. Stable late hypertension coexisted with highly elevated levels of Ang II-positive cells in the cortical tubulointerstitium, enhanced increase in the expression of p47phox (NADPH oxidase regulatory subunit), marked down-regulation of COX-2 expression, expanded plasma volume and decreased creatinine clearance. These alterations were reduced when the dams were given α-tocopherol during lactation. The offspring of well-nourished dams treated with α-tocopherol exhibited most of the alterations encountered in the offspring of undernourished dams not treated with α-tocopherol. Thus, alterations in proximal tubule Na+ transport, subcellular signalling pathways and reactive oxygen species handling in renal tissue underpin the development of hypertension.
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Pernambuco, Professor Moraes Rego Avenue, Cidade Universitária, Recife 50670-901, Brazil.
authors.forename: Leucio D
authors.initials: LD
authors.lastname: Vieira-Filho
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Pernambuco, Professor Moraes Rego Avenue, Cidade Universitária, Recife 50670-901, Brazil.
authors.forename: Edjair V
authors.initials: EV
authors.lastname: Cabral
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Pernambuco, Professor Moraes Rego Avenue, Cidade Universitária, Recife 50670-901, Brazil.
authors.forename: Juliane S
authors.initials: JS
authors.lastname: Farias
authors.affiliation: National Institute of Science and Technology for Structural Biology and Bioimaging, Rio de Janeiro, Brazil.
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Silva
authors.affiliation: National Institute of Science and Technology for Structural Biology and Bioimaging, Rio de Janeiro, Brazil.
authors.forename: Humberto
authors.initials: H
authors.lastname: Muzi-Filho
authors.affiliation: National Institute of Science and Technology for Structural Biology and Bioimaging, Rio de Janeiro, Brazil.
authors.forename: Adalberto
authors.initials: A
authors.lastname: Vieyra
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Pernambuco, Professor Moraes Rego Avenue, Cidade Universitária, Recife 50670-901, Brazil.
authors.forename: Ana D O
authors.initials: AD
authors.lastname: Paixão
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D015536:Down-Regulation; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D044342:Malnutrition / Q000150:complications / Q000503:physiopathology*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000009:adverse effects*; D024502:alpha-Tocopherol / Q000008:administration & dosage
chemical_list: D027682:Cation Transport Proteins; D017382:Reactive Oxygen Species; D011945:Receptors, Angiotensin; D012982:Sodium, Dietary; D000804:Angiotensin II; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D019255:NADPH Oxidases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000251:Adenosine Triphosphatases; C021838:sodium-translocating ATPase; D005978:Glutathione; D024502:alpha-Tocopherol