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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/F1371    most recent 00378.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Machura, K. Articles by Kurtz, A. PubMed PubMed Citation Articles by Machura, K. Articles by Kurtz, A.

Developmental renin expression in mice with a defective renin-angiotensin system

¹Institute of Physiology, University of Regensburg, Regensburg; ; ²Max-Delbrück-Center for Molecular Medicine, Berlin, ; ³Department of Medicine, Duke University Medical Center, Durham, North Carolina; and ; ⁴Department of Nephrology and Hypertension, Friedrich Alexander University, Erlangen-Nürnberg, Germany

Submitted July 6, 2009 ; accepted in final form August 20, 2009

During nephrogenesis, renin expression shifts from the vessel walls of interlobular arteries to the terminal portions of afferent arterioles in a wavelike pattern. Since the mechanisms responsible for the developmental deactivation of renin expression are as yet unknown, we hypothesized that the developing renin-angiotensin 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 ANG II AT_1a, AT_1b, or AT₂ receptors and in animals with abolished circulating ANG II due to deletion of the gene for angiotensin I-converting enzyme (ACE). The development of intrarenal renin expression was normal in mice lacking ANG II AT_1b or AT₂ receptors. In animals lacking both ANG II AT_1a and AT_1b receptors, ACE, or ANG II AT_1a 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 grapelike 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 ANG II 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 AT_1a receptors. However, the distribution pattern of renin cells in adult kidneys with an interrupted RAS does not mimic any normal developmental stage since renin expression is frequently found in cells outside the arteriolar vessel walls in RAS mutants.

development; angiotensin II