ACE inhibition modulates transforming growth factor-beta receptors in the young rat.
The renin-angiotensin system plays an important role in renal growth and development. Exposure of the neonate to angiotensin converting enzyme (ACE) inhibitors increases mortality and results in growth retardation and abnormal renal development. It has been demonstrated that ACE inhibition in the developing kidney reduces the renal expression of growth factors, which may account for renal growth impairment. This study was designed to investigate the relationship between renal growth impairment and the expression of transforming growth factor-beta1 (TGF-beta1), TGF-beta receptor I [TbetaRI, activin-like kinase (ALK)-1 and ALK-5], and TGF-beta receptor II (TbetaRII). Newborn rat pups were treated with enalapril (30 mg/kg per day) or vehicle for 7 days, and kidneys were removed for Western blotting of TGF-beta1, ALK-1, ALK-5, and TbetaRII, and for RT-PCR of ALK-5 and TbetaRII. TGF-beta1, ALK-1, ALK-5, and TbetaRII were also detected by immunohistochemistry. Enalapril treatment resulted in an increased mortality (30.4%) by day 7, and reduced body weight and kidney weight ( P<0.05 versus vehicle). Enalapril decreased renal TGF-beta1, ALK-1, and ALK-5 protein expression ( P<0.05). Also, enalapril decreased ALK-5 mRNA expression ( P<0.05). TbetaRII expression was not changed by enalapril treatment. These results indicate that ACE inhibition in the developing kidney decreases TGF-beta1, ALK-1, and ALK-5 expression, which may account for renal growth impairment. TbetaRII may not be modulated by ACE inhibition in the developing kidney.
Kang
Nam Soo
NS
Department of Pediatrics, Korea University, Seoul, Korea.
Yim
Hyung Eun
HE
Bae
In Sun
IS
Choi
Jeong Hoon
JH
Choi
Byung Min
BM
Yoo
Kee Hwan
KH
Hong
Young Sook
YS
Lee
Joo Won
JW
Kim
Soon Kyum
SK
D030201:Activin Receptors, Type I / Q000235:genetics; D000367:Age Factors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D018125:Receptors, Transforming Growth Factor beta; D004656:Enalapril; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat