Altered renin-angiotensin system gene expression causes renal hypoplasia in the rats with nitrofen-induced diaphragmatic hernia.
The association between renal hypoplasia and pulmonary hypoplasia in congenital diaphragmatic hernia (CDH) has become recently appreciated. However, the underlying mechanisms responsible for this association are still unknown. Renin-angiotensin system (RAS) plays an important role in renal and somatic growth, angiogenesis and reproduction. We hypothesized that abnormal expression of RAS components may be responsible for renal hypoplasia in CDH. We therefore designed this study to examine the gene expression of main components of RAS in the kidney of nitrofen-induced CDH in the rat. Pregnant rats were exposed to either olive oil or 100 mg of nitrofen on day 9.5 of gestation. Foetuses were recovered at term and divided into three groups: control (n=8), nitrofen without CDH (n=8) and CDH (n=8). Reverse transcription polymerase chain reaction was performed to evaluate the relative amount of angiotensinogen (AGT), angiotensin II type 1 receptor with 1a and 1b subtypes (AT(1a)R and AT(1b)R), angiotensin II type 2 receptor (AT(2)R), angiotensin-converting enzyme (ACE) and renin expression in the kidney. AT(1a)R, AT(1b)R, AT(2)R, AGT and renin levels were significantly decreased in the kidney of CDH rats compared with controls. We did not find a significant difference in ACE between CDH animals and controls. Our data show that the downregulation of RAS may play an important role in the pathogenesis of renal hypoplasia in the nitrofen-induced CDH.
Chertin
Boris
B
Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin 12, Ireland.
Nakazawa
Nana
N
Montedonico
Sandra
S
Shima
Hideki
H
Puri
Prem
P
D000015:Abnormalities, Multiple / Q000196:embryology*; D000818:Animals; D015536:Down-Regulation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006548:Hernia, Diaphragmatic / Q000196:embryology*; D065630:Hernias, Diaphragmatic, Congenital; D007668:Kidney / Q000002:abnormalities* / Q000196:embryology*; D010647:Phenyl Ethers; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000235:genetics*
D010647:Phenyl Ethers; C007350:nitrofen