Developmental renin expression in mice with defective renin angiotensin system

Item Type:	Article
Title:	Developmental renin expression in mice with defective renin angiotensin system
Creators Name:	Machura, K. and Steppan, D. and Neubauer, B. and Alenina, N. and Coffman, T.M. and Facemire, C.M. and Hilgers, K.F. and Eckardt, K.U. and Wagner, C. and Kurtz, A.
Abstract:	During nephrogenesis, renin expression shifts from the vessel walls of interlobular arteries to the terminal portions of afferent arterioles in a wave-like pattern. Since the mechanisms responsible for the developmental deactivation of renin expression are as yet unknown, we hypothesized that the developing renin-angiontensin-system (RAS) may downregulate itself via negative feedback to prevent overactivity of renin. To test for a possible role of angiotensin II in the developmental deactivation of renin expression, we studied the development of intrarenal renin expression in mice lacking ANGII-AT1a, -AT1b or -AT2 receptors and in animals with abolished circulating ANGII due to deletion of the gene for angiotensin I-converting enzyme (ACE). The development of intrarenal renin expression was normal in mice lacking ANGII-AT1b or -AT2 receptors. In animals lacking both ANGII-AT1a and -1b receptors, ACE or ANGII-AT1a receptors, renin expression was normal early and renin disappeared from mature vessels until development of cortical interlobular and afferent arterioles began. The development of cortical vessels in these genotypes was accompanied by a markedly increased number of renin-expressing cells, many of which were ectopically located and attached in a grape-like fashion to the outer vessel perimeter. Although the number of renin-expressing cells declined during final maturation of the kidneys, the atypical distribution pattern of renin cells was maintained. These findings suggest that ANGII does not play a central role in the typical developmental shift in renin expression from the arcuate vessels to the afferent arterioles. During postnatal maturation of mouse kidneys, interruption of the RAS causes severe hyperplasia of renin cells via a mechanism that centrally involves AT1a receptors. However, the distribution pattern of renin cells in adult kidneys with an interrupted renin angiotensin system does not mimic any normal developmental stage since renin expression is frequently found in cells outside the arteriolar vessel walls in RAS mutants.
Keywords:	Renin, Development, Angiotensin, Renin Angiotensin System, Animals, Mice
Source:	American Journal of Physiology Renal Physiology
ISSN:	1931-857X
Publisher:	American Physiological Society
Volume:	297
Number:	5
Page Range:	F1371-F1380
Date:	November 2009
Official Publication:	https://doi.org/10.1152/ajprenal.00378.2009
PubMed:	View item in PubMed

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