Anne R. Tinning

Boye L. Jensen

Carev D

Cha JH

Daian Chen

Gerber HP

Iben Johnsen

Kirsten Madsen

Speller AM

Thomas M. Coffman

Tufro A

Yuan HT

Postnatal inhibition or deletion of angiotensin II (ANG II) AT1receptors impairs renal medullary mircrovascular development through a mechanism that may include vascular endothelial growth factor (VEGF). The present study was designed to test if VEGF/VEGF receptor signaling is necessary for the development of the renal medullary microcirculation. Endothelial cell-specific immunolabeling of kidney sections from rats showed immature vascular bundles at postnatal day (P) 10 with subsequent expansion of bundles until P21. Medullary VEGF protein abundance coincided with vasa recta bundle formation. In human fetal kidney tissue, immature vascular bundles appeared early in the third trimester (GA27-28) and expanded in size until term. Rat pups treated with the VEGF receptor-2 (VEGFR2) inhibitor vandetanib (100 mg·kg−1·day−1) from P7 to P12 or P10 to P16 displayed growth retardation and proteinuria. Stereological quantification showed a significant reduction in total length (386 ± 13 vs. 219 ± 16 m), surface area, and volume of medullary microvessels. Vascular bundle architecture was unaffected. ANG II-AT1A/1B−/−mice kidneys displayed poorly defined vasa recta bundles whereas mice with collecting duct principal cell-specific AT1Adeletion displayed no medullary microvascular phenotype. In conclusion, VEGFR2 signaling during postnatal development is necessary for expansion of the renal medullary microcirculation but not structural patterning of the vasa recta bundles, which occurs through an AT1-mediated mechanism.</jats:p

Crossref

AJP Renal Physiology

Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development

Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development

Abstract

Similar works

Full text

Available Versions

Crossref