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Angiotensin II promotes development of the renal microcirculation through AT1 receptors.

Authors: Madsen, K  Marcussen, N  Pedersen, M  Kjaersgaard, G  Facemire, C  Coffman, TM  Jensen, BL 
Citation: Madsen K, etal., J Am Soc Nephrol. 2010 Mar;21(3):448-59. doi: 10.1681/ASN.2009010045. Epub 2010 Jan 7.
Pubmed: (View Article at PubMed) PMID:20056745
DOI: Full-text: DOI:10.1681/ASN.2009010045

Pharmacologic or genetic deletion of components of the renin-angiotensin system leads to postnatal kidney injury, but the roles of these components in kidney development are unknown. To test the hypothesis that angiotensin II supports angiogenesis during postnatal kidney development, we quantified CD31(+) postglomerular microvessels, performed quantitative PCR analysis of vascular growth factor expression, and measured renal blood flow by magnetic resonance. Treating rats with the angiotensin II type 1 receptor antagonist candesartan for 2 weeks after birth reduced the total length, volume, and surface area of capillaries in both the cortex and the medulla and inhibited the organization of vasa recta bundles. In addition, angiotensin II type 1 antagonism inhibited the transcription of angiogenic growth factors vascular endothelial growth factor, angiopoietin-1, angiopoietin-2, and the angiopoietin receptor Tie-2 in cortex and medulla. Similarly, Agtr1a(-/-);Agtr1b(-/-) mouse kidneys had decreased angiopoietin-1, angiopoietin-2, and Tie-2 mRNAs at postnatal day 14. To test whether increased urinary flow leads to microvascular injury, we induced postnatal polyuria with either lithium or adrenalectomy, but these did not alter vascular endothelial growth factor expression or vasa recta organization. Compared with vehicle-treated rats, renal blood flow was significantly (approximately 20%) lower in candesartan-treated rats even 14 days after candesartan withdrawal. Taken together, these data demonstrate that angiotensin II promotes postnatal expansion of postglomerular capillaries and organization of vasa recta bundles, which are necessary for development of normal renal blood flow.

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CRRD Object Information
CRRD ID: 8554659
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.