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Messerschmidt and Wifes Foundation"},{"DOI":"10.13039\/501100004915","name":"Danish Kidney Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004915","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Familien Hede Nielsens Foundation"},{"name":"Krista and Viggo Petersens Foundation"},{"name":"Else and Mogens Wedell Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2016,9,1]]},"abstract":"<jats:p>Postnatal inhibition or deletion of angiotensin II (ANG II) AT<jats:sub>1<\/jats:sub>receptors 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\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>) from P7 to P12 or P10 to P16 displayed growth retardation and proteinuria. Stereological quantification showed a significant reduction in total length (386 \u00b1 13 vs. 219 \u00b1 16 m), surface area, and volume of medullary microvessels. Vascular bundle architecture was unaffected. ANG II-AT<jats:sub>1A\/1B<\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup>mice kidneys displayed poorly defined vasa recta bundles whereas mice with collecting duct principal cell-specific AT<jats:sub>1A<\/jats:sub>deletion 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 AT<jats:sub>1<\/jats:sub>-mediated mechanism.<\/jats:p>","DOI":"10.1152\/ajprenal.00221.2016","type":"journal-article","created":{"date-parts":[[2016,7,14]],"date-time":"2016-07-14T06:37:07Z","timestamp":1468478227000},"page":"F586-F599","source":"Crossref","is-referenced-by-count":9,"title":["Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development"],"prefix":"10.1152","volume":"311","author":[{"given":"Anne R.","family":"Tinning","sequence":"first","affiliation":[{"name":"Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boye 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