MAPK and angiotensin II receptor in kidney of newborn rats from losartan-treated dams.
Several lines of evidence suggest that angiotensin II (A-II) participates in the postnatal development of the kidney in rats. Many effects of A-II are mediated by mitogen-activated protein kinase (MAPK) pathways. This study investigated the influence that treatment with losartan during lactation has on MAPKs and on A-II receptor types 1 (AT(1)) and 2 (AT(2)) expression in the renal cortices of the offspring of dams exposed to losartan during lactation. In addition, we evaluated the relationship between such expression and changes in renal function and structure. Rat pups from dams receiving 2% sucrose or losartan diluted in 2% sucrose (40 mg/dl) during lactation were killed 30 days after birth, and the kidneys were removed for histological, immunohistochemical, and Western blot analysis. AT(1) and AT(2) receptors and p-p38, c-Jun N-terminal kinases (p-JNK) and extracellular signal-regulated protein kinases (p-ERK) expression were evaluated using Western blot analysis. The study-group rats presented an increase in AT(2) receptor and MAPK expression. In addition, these rats also presented lower glomerular filtration rate (GFR), greater albuminuria, and changes in renal structure. In conclusion, newborn rats from dams exposed to losartan during lactation presented changes in renal structure and function, which were associated with AT(2) receptor and MAPK expression in the kidneys.
Department of Physiology, University of São Paulo School of Medicine, Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil.
Ana Paula Coelho
AP
Balbi
Evelyn Cristina Santana
EC
Marin
Heloisa Della Coletta
HD
Francescato
Roberto Silva
RS
Costa
Terezila Machado
TM
Coimbra
D000199:Actins / Q000032:analysis; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases / Q000032:analysis; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D019808:Losartan / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000032:analysis*
D000199:Actins; D047228:Angiotensin II Type 1 Receptor Blockers; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019808:Losartan; D011945:Receptors, Angiotensin; C498862:Acta2 protein, rat