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Developmental renin expression in mice with a defective renin-angiotensin system.
Am J Physiol Renal Physiol. 2009 Nov; 297(5):F1371-80.AJ

Abstract

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 AT1a, AT1b, 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 AT1b or AT2 receptors. In animals lacking both ANG II AT1a and AT1b receptors, ACE, or ANG II 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 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.

Authors+Show Affiliations

Institute of Physiology, University of Regensburg, Regensburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19710239

Citation

Machura, Katharina, et al. "Developmental Renin Expression in Mice With a Defective Renin-angiotensin System." American Journal of Physiology. Renal Physiology, vol. 297, no. 5, 2009, pp. F1371-80.
Machura K, Steppan D, Neubauer B, et al. Developmental renin expression in mice with a defective renin-angiotensin system. Am J Physiol Renal Physiol. 2009;297(5):F1371-80.
Machura, K., Steppan, D., Neubauer, B., Alenina, N., Coffman, T. M., Facemire, C. S., Hilgers, K. F., Eckardt, K. U., Wagner, C., & Kurtz, A. (2009). Developmental renin expression in mice with a defective renin-angiotensin system. American Journal of Physiology. Renal Physiology, 297(5), F1371-80. https://doi.org/10.1152/ajprenal.00378.2009
Machura K, et al. Developmental Renin Expression in Mice With a Defective Renin-angiotensin System. Am J Physiol Renal Physiol. 2009;297(5):F1371-80. PubMed PMID: 19710239.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Developmental renin expression in mice with a defective renin-angiotensin system. AU - Machura,Katharina, AU - Steppan,Dominik, AU - Neubauer,Bjoern, AU - Alenina,Natalia, AU - Coffman,Thomas M, AU - Facemire,Carie S, AU - Hilgers,Karl F, AU - Eckardt,Kai-Uwe, AU - Wagner,Charlotte, AU - Kurtz,Armin, Y1 - 2009/08/26/ PY - 2009/8/28/entrez PY - 2009/8/28/pubmed PY - 2009/11/18/medline SP - F1371 EP - 80 JF - American journal of physiology. Renal physiology JO - Am. J. Physiol. Renal Physiol. VL - 297 IS - 5 N2 - 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 AT1a, AT1b, 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 AT1b or AT2 receptors. In animals lacking both ANG II AT1a and AT1b receptors, ACE, or ANG II 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 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. SN - 1522-1466 UR - https://www.unboundmedicine.com/medline/citation/19710239/Developmental_renin_expression_in_mice_with_a_defective_renin_angiotensin_system_ L2 - http://journals.physiology.org/doi/full/10.1152/ajprenal.00378.2009?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -