Korean J Pediatr.  2016 Jan;59(1):8-15. 10.3345/kjp.2016.59.1.8.

Impaired angiogenesis in the enalapril-treated neonatal rat kidney

• Yim HE
• Yoo KH
• Bae ES
• Hong YS
• Lee JW

• KMID: 2152939
• DOI: http://doi.org/10.3345/kjp.2016.59.1.8

Abstract

PURPOSE
Nephrogenesis is normally accompanied by a tightly regulated and efficient vascularization. We investigated the effect of angiotensin II inhibition on angiogenesis in the developing rat kidney.
METHODS
Newborn rat pups were treated with enalapril (30 mg/kg/day) or vehicle (control) for 7 days after birth. Renal histological changes were checked using Hematoxylin & Eosin staining. We also investigated the intrarenal expression of vascular endothelial growth factor (VEGF)-A, VEGF receptor 1 (VEGFR1), VEGFR2, platelet-derived growth factor (PDGF)-B, and PDGF receptor-beta with Western blotting and immunohistochemical staining at postnatal day 8. Expression of the endothelial cell marker CD31 was examined to determine glomerular and peritubular capillary density.
RESULTS
Enalapril-treated rat kidneys showed disrupted tubules and vessels when compared with the control rat kidneys. In the enalapril-treated group, intrarenal VEGF-A protein expression was significantly higher, whereas VEGFR1 protein expression was lower than that in the control group (P<0.05). The expression of VEGFR2, PDGF-B, and PDGF receptor-beta was not different between the 2 groups. The increased capillary CD31 expression on the western blots of enalapril-treated rat kidneys indicated that the total endothelial cell protein level was increased, while the cortical capillary density, assessed using CD31 immunohistochemical staining, was decreased.
CONCLUSION
Impaired VEGF-VEGFR signaling and altered capillary repair may play a role in the deterioration of the kidney vasculature after blocking of angiotensin II during renal development.

Keyword

Angiotensin II; Growth and development; Vascular remodeling

MeSH Terms

Angiotensin II
Animals
Blotting, Western
Capillaries
Enalapril
Endothelial Cells
Eosine Yellowish-(YS)
Growth and Development
Hematoxylin
Humans
Infant, Newborn
Kidney*
Parturition
Platelet-Derived Growth Factor
Rats*
Receptors, Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor A
Angiotensin II
Enalapril
Eosine Yellowish-(YS)
Hematoxylin
Platelet-Derived Growth Factor
Receptors, Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor A