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http://dx.doi.org/10.3345/kjp.2016.59.1.8

Impaired angiogenesis in the enalapril-treated neonatal rat kidney  

Yim, Hyung Eun (Department of Pediatrics, Korea University College of Medicine)
Yoo, Kee Hwan (Department of Pediatrics, Korea University College of Medicine)
Bae, Eun Soo (Department of Pediatrics, Korea University College of Medicine)
Hong, Young Sook (Department of Pediatrics, Korea University College of Medicine)
Lee, Joo Won (Department of Pediatrics, Korea University College of Medicine)
Publication Information
Clinical and Experimental Pediatrics / v.59, no.1, 2016 , pp. 8-15 More about this Journal
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.
Keywords
Angiotensin II; Growth and development; Vascular remodeling;
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