Vascular versus tubular renin: role in kidney development. Am J Physiol Regul Integr Comp Physiol 2015 Sep 15;309(6):R650-7
Date
08/08/2015Pubmed ID
26246508Pubmed Central ID
PMC4591368DOI
10.1152/ajpregu.00313.2015Scopus ID
2-s2.0-84941764098 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
Renin, the key regulated enzyme of the renin-angiotensin system regulates blood pressure, fluid-electrolyte homeostasis, and renal morphogenesis. Whole body deletion of the renin gene results in severe morphological and functional derangements, including thickening of renal arterioles, hydronephrosis, and inability to concentrate the urine. Because renin is found in vascular and tubular cells, it has been impossible to discern the relative contribution of tubular versus vascular renin to such a complex phenotype. Therefore, we deleted renin independently in the vascular and tubular compartments by crossing Ren1(c fl/fl) mice to Foxd1-cre and Hoxb7-cre mice, respectively. Deletion of renin in the vasculature resulted in neonatal mortality that could be rescued with daily injections of saline. The kidneys of surviving mice showed the absence of renin, hypertrophic arteries, hydronephrosis, and negligible levels of plasma renin. In contrast, lack of renin in the collecting ducts did not affect kidney morphology, intra-renal renin, or circulating renin in basal conditions or in response to a homeostatic stress, such as sodium depletion. We conclude that renin generated in the renal vasculature is fundamental for the development and integrity of the kidney, whereas renin in the collecting ducts is dispensable for normal kidney development and cannot compensate for the lack of renin in the vascular compartment. Further, the main source of circulating renin is the kidney vasculature.
Author List
Sequeira-Lopez ML, Nagalakshmi VK, Li M, Sigmund CD, Gomez RAAuthor
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlood Vessels
Body Weight
Forkhead Transcription Factors
Genotype
Homeodomain Proteins
Kidney
Kidney Tubules
Mice
Mice, Knockout
Organ Size
Renin
Renin-Angiotensin System