Korean J Pediatr.  2004 Mar;47(3):325-331.

Angiotensin Converting Enzyme Inhibition Modulates Mitogen Activated Protein Kinase Family Expressions in the Neonatal Rat Kidney

• Choi BM
• Oh MH
• Yoo KH

Abstract

PURPOSE
In a developing kidney, the renin-angiotensin system(RAS) is markedly activated and is thought to play an important role in postnatal renal growth and maturation. We previously demonstrated that angiotensin converting enzyme(ACE) inhibition in a developing rat kidney increases apoptosis and decreases its related gene expressions, which may account for renal growth impairment. Among the mitogen-activated protein kinases(MAPK) family members, c-jun N terminal kinase(JNK) and p38 MAPK(p38) are thought to inhibit cell growth and induce apoptosis. This study was designed to investigate the relationship between the RAS and the MAPK family during neonatal renal development.
METHODS
Forty-nine neonatal Spargue-Dawley rats were separated into two groups. The enalapril group was treated with ACE inhibitor(enalapril:30 mg/kg/day) and the control group with normal saline for seven days. Their kidneys were removed for immunohistochemical stain and western blot analysis of JNK-2 and p38.
RESULTS
In the enalapril group, JNK-2 expression was strongly detected in the dilated cortical tubular epithelial cells, and JNK-2 protein expression was significantly increased compared to the control group. p38 expression was noted in the dilated tubular epithelial cells by ACE inhibitor and also p38 protein expression was significantly increased.
CONCLUSION
These results suggest that the expressions of the MAPK family, especially JNK and p38, are modulated by ACE inhibition in the neonatal rat kidney. In regard of the correlation between MAPK activations and the occurrence of apoptosis in renal growth impairment by ACE inhibition, JNK and p38 may be implicated to participate in angiotensin II related intracellular signaling pathways of renal apoptosis in developing kidney.

Keyword

Renin angiotensin system; Angiotensin ii; Angiotensin converting enzyme; Mitogen-activated protein kinases; c-Jun NH2-terminal kinase; p38 mitogen-activated protein kinases; Kidney; Animal model; Rat

MeSH Terms

Angiotensin II
Angiotensins*
Animals
Apoptosis
Blotting, Western
Enalapril
Epithelial Cells
Gene Expression
Humans
Kidney*
Mitogen-Activated Protein Kinases
Models, Animal
p38 Mitogen-Activated Protein Kinases
Peptidyl-Dipeptidase A*
Protein Kinases*
Rats*
Renin-Angiotensin System
Angiotensin II
Angiotensins
Enalapril
Mitogen-Activated Protein Kinases
Peptidyl-Dipeptidase A
Protein Kinases
p38 Mitogen-Activated Protein Kinases